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Bazaz, Rohit. "The effect of Streptococcus pneumoniae pneumonia on atherosclerosis." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/16897/.
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Koppe, Uwe Moritz Eberhard. "Role of type I interferons in Streptococcus pneumoniae pneumonia." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16532.
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Streptococcus pneumoniae ist die häufigste Ursache für ambulant erworbene Pneumonien weltweit. Daher müssen die Wirts-Pathogen-Interaktionen erforscht werden, um neue Therapiestrategien zu entwickeln. In dieser Studie habe ich 1. den Typ I Interferon (IFN)-stimulierenden Signalweg des angeborenen Immunsystems in Pneumokokken-infizierten Wirtszellen sowie 2. dessen Bedeutung in der Pneumokokkenpneumonie untersucht. Humane und murine Makrophagen, aber nicht alveolare Epithelzellen, produzierten Typ I IFNs nach Infektion mit S. pneumoniae. Dieses war abhängig vom Virulenzfaktor Pneumolysin und erforderte sowohl die Phagozytose der Bakterien als auch die Ansäuerung der Endosomen. Die Induktion der Typ I IFNs wird durch einen zytosolischen Signalweg vermittelt, welcher wahrscheinlich DNA erkennt und sowohl das Adapterprotein STING als auch den Transkriptionsfaktor IRF3 aktiviert. Typ I IFNs, welche von infizierten Makrophagen gebildet wurden, regulierten die Expression von IFN-stimulierten Genen (ISGs) und Chemokinen in Makrophagen und co-kultivierten alveolaren Epithelzellen in vitro und in Mauslungen in vivo. In einem murinen Pneumoniemodell hatten die Typ I IFNs jedoch einen negativen Effekt für den Wirt. Mäuse mit einem Defekt im Typ I IFN-Rezeptor oder mit einem Knockout im Typ I und Typ II IFN-Rezeptor hatten eine signifikant geringere Bakterienlast in der Lunge und eine verminderte Reduktion der Körpertemperatur und des Körpergewichtes als wild-typ Mäuse. Diese Effekte waren nicht durch Änderungen in der Zellrekrutierung oder durch Änderungen der Zytokin-/Chemokinexpression erklärbar. Zusammenfassend lässt sich feststellen, dass Typ I IFNs durch Pneumokokken induziert werden, aber dass sie trotz einiger positiver Effekte auf die Expression von ISGs einen negativen Gesamteffekt in einem murinen Pneumoniemodell aufweisen. Ein detailliertes Verständnis der Typ I IFN-Antwort während der Pneumokokkeninfektion kann die Entwicklung neuer Therapiestrategien unterstützen.<br>Streptococcus pneumoniae is the leading cause of community-acquired pneumonia world-wide. A detailed understanding of the host-pathogen interactions is required in order to foster the development of new therapeutic strategies. Here, I (I) characterized an innate immune recognition pathway that senses pneumococcal infection and triggers the production of type I interferons (IFNs), and (II) examined the role of type I IFNs in pneumococcal pneumonia in mice. Human and murine macrophages, but not alveolar epithelial cells, produced type I IFNs after infection with S. pneumoniae. This induction was dependent on the virulence factor pneumolysin, the phagocytosis of the bacteria, and the acidification of the endosome. Moreover, it appeared to be mediated by a cytosolic DNA-sensing pathway involving the adaptor molecule STING and the transcription factor IRF3. Type I IFNs produced by S. pneumoniae-infected macrophages positively regulated the expression of IFN-stimulated genes (ISGs) and chemokines in macrophages and co-cultured alveolar epithelial cells in vitro and in mouse lungs in vivo. However, in a murine model of pneumococcal pneumonia, type I IFN signaling was detrimental to the host defense. Mice deficient in the type I IFN signaling or double deficient in type I and type II IFN signaling had a significantly reduced bacterial load in the lung and a diminished reduction of body temperature and body weight compared to wild-type mice. The decreased susceptibility of the knockout mice was unlikely to be attributable to alterations in cell recruitment or cytokine/chemokine production. In conclusion, type I IFNs are induced during pneumococcal infection. However, despite their positive effects on the expression of some ISGs and chemokines, they negatively affect the outcome of pneumococcal pneumonia in an in vivo mouse model. Targeting the type I IFN system could potentially be an effective way in enhancing the immune response in patients with S. pneumoniae pneumonia.
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Bracht, Dagmar. "Proteomanalyse von Streptococcus pneumoniae." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=977729931.
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McNamee, Lynnelle Ann. "Effects of a primary influenza infection on susceptibility to a secondary Streptococcus pneumoniae infection." Diss., Montana State University, 2006. http://etd.lib.montana.edu/etd/2006/mcnamee/McNameeL1206.pdf.
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Koo, Kun, and 古軍. "Vancomycin tolerance in streptococcus pneumoniae." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970588.
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Wyres, Kelly L. "Genome evolution in Streptococcus pneumoniae." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:985b1fc6-c1a9-41b3-a20a-1735329d962b.
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Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen responsible for >1.6 million annual deaths globally. Pneumococcal penicillin-resistance is conferred by acquisition of ‘altered’ penicillin-binding protein (pbp) genes. The first penicillin-nonsusceptible pneumococci were identified in the late 1960s. Global pneumococcal penicillin-nonsusceptibility rates rapidly increased in the 1980s/90s. Since 2000, protein-conjugate vaccines, targeting 7, 10 or 13 of the ≥94 different pneumococcal capsule types (serotypes), have been introduced in many countries. Following vaccine implementation there has been a decline in vaccine-type pneumococcal disease and an increase in non-vaccine-type disease. These epidemiological changes result from “serotype replacement” and/or “serotype switching”. The former describes the expansion of non-vaccine-type clones in the absence of vaccine-type pneumococci. The latter describes serotype change following recombination at the capsule polysaccharide synthesis (cps) locus. To fully understand how pneumococci respond to vaccine- and antibiotic-induced selective pressures, we must better understand the evolutionary history of this pathogen. This thesis describes the study of a global collection of 426 pneumococci, dated 1937 - 2007. Serotype, genotype and penicillin-susceptibility data were collected. Nucleotide sequences of three pbp genes (for 389 isolates) and whole-genome sequences (for 96 isolates) were also generated. The data demonstrated the long-term persistence of certain clones within pneumococcal populations, and that pbp and large-fragment (>30 kb) cps ± pbp recombination was occurring prior to both widespread antibiotic use and vaccine implementation. The data highlighted the promiscuous nature of the globally-distributed PMEN1 clone and its contribution to the spread of pneumococcal penicillin-resistance. PMEN1 also donated multiple, large regions (1.7 - 32.3 kb) of its genome to at least two un-related clones. Finally, six “Tn916-like” genetic elements, conferring resistance to non-penicillin antibiotics, were newly identified. These included two of the oldest ever described. These results provided a unique insight into the history of pneumococcal evolution and the importance of genetic recombination.
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Rudmann, Emily. "Parsing the Streptococcus pneumoniae virulome." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108795.
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Thesis advisor: Tim van Opijnen<br>Streptococcus pneumoniae is a prominent gram-positive commensal and opportunistic pathogen which possesses a large pan-genome. Significant strain-to-strain variability in genomic content drives the use of varied pathways to perform similar processes between strains. Considering this variation, we employ a set of 36 strains, representative of 78% of total pan-genome diversity, with which to perform functional studies. We previously determined the set of genes required by 22 of the 36 strains to maintain successful infection in a host, or the virulome. In this work, we sought to parse from the virulome the genes required specifically for nasopharyngeal adhesion, a crucial step in S. pneumoniae colonization and transmission, and often a precursor to invasive disease, as well as gene requirements for subversion of the macrophage. We performed in vitro attachment Tn-seq in the 22 strains to D562 human nasopharyngeal epithelial cells, identifying thirteen factors that exhibit requirements for adhesion, and preliminarily validated a proposed universal requirement for survival of the macrophage by a killing assay using J774A.1 murine migratory macrophages<br>Thesis (BS) — Boston College, 2020<br>Submitted to: Boston College. College of Arts and Sciences<br>Discipline: A&S Honors<br>Discipline: Biology
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Koo, Kun. "Vancomycin tolerance in streptococcus pneumoniae." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25139216.
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Alghofaili, Fayez Abdullah. "Streptococcus pneumoniae-stress hormone interactions." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/41267.
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Streptococcus pneumoniae is one of the most important bacterial pathogens of humans causing a wide range of mild to life-threating diseases. It is also a commensal microorganism in the nasopharynx of up to 60% of people. Fundamental aspects of its ability for transition from colonisation to an infectious state as well as how bacterial-host interactions influence this process are largely unknown. In the field of microbial endocrinology, it has been well established in mainly Gram-negative bacteria that stress hormones such as norepinephrine epinephrine and dopamine play an essential role in determining the outcome of bacterial infections. This study successfully established the conditions to investigate S. pneumoniae-stress hormone interactions using modified serum-SAPI media. 13 mutants lacking two-component regulatory system and 4 two-component system fusion reporter strains were created, and examined for their role in S. pneumoniae-stress hormone interactions. This study demonstrated that S. pneumoniae is stress hormone responsive and has mechanisms to recognise and process host stress hormones by a transferrin-iron delivery mechanism, which evidence suggests might be mediated via the TCS09 system since hormone-induced growth and radiolabelled norepinephrine and Fe uptake were reduced in a ΔTCS09 mutant. In addition, the pneumococcal response to stress hormone exposure resulted in a change in cell-cell association from chains into diplococci and cell morphology by reducing cell size and the capsule. Furthermore, the pneumococcal exposure to norepinephrine also increased biofilm formation and significantly altered metabolism. The analysis of in vivo experiments indicated that a stress hormone encounter might trigger translocation from the nasopharynx into the lungs, which may enhance S. pneumoniae in its transition from commensal to pathogen. Therefore, the pneumococcal ability to respond to host stress signals may be key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis.
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Abdeldaim, Guma M. K. "PCR detection of Streptococcus pneumoniae and Haemophilus influenzae in pneumonia patients." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl.[distributör], 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107931.
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Silva, Júnior Jailton de Azevedo. "Estudo da colonização nasofaringeana por Streptococcus pneumoniae em crianças com suspeita clínica de pneumonia." reponame:Repositório Institucional da FIOCRUZ, 2011. https://www.arca.fiocruz.br/handle/icict/4220.
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Previous issue date: 2011<br>Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil<br>Streptococcus pneumoniae constitui um dos mais importantes patógenos
bacterianos do trato respiratório, podendo causar infecções invasivas e não
invasivas, levando a altas taxas de morbi-mortalidade, particularmente em crianças
menores de cinco anos de idade. A bactéria ganha acesso ao hospedeiro através da
colonização da nasofaringe, que representa um importante reservatório para a
transmissão deste patógeno na comunidade, contribuindo para a disseminação
horizontal de S. pneumoniae entre os indivíduos de uma população. No presente
estudo, procuramos caracterizar o perfil de colonização nasofaringeana por S.
pneumoniae em pacientes menores de cinco anos de idade com suspeita clínica de
pneumonia, atendidos na Unidade de Saúde de São Marcos, Bairro de Pau da Lima,
Salvador, no ano de 2009. Um total de 205 swabs foram coletados entre as crianças
consideradas elegíveis para o estudo. Os isolados de S. pneumoniae foram
identificados através de métodos microbiológicos clássicos e a determinação do
sorogrupo/sorotipo foi realizada empregando-se a técnica de Multiplex-PCR. A
sensibilidade a sete antimicrobianos foi testada através da técnica de microdiluição
em caldo, sendo que os isolados com CIM para penicilina ≥ 0,125 μg/mL foram
considerados não-susceptíveis. A técnica de PFGE foi realizada para 26 isolados
correspondentes aos sorotipos mais frequentes e associados a não-sensibilidade à
penicilina (sorotipos 14, 19F e 23F). Um total de 72 (35,1%) crianças foram
diagnosticadas com pneumonia, sendo 39 (54,2%) menores de dois anos de idade.
A taxa de colonização geral foi de 50,2%, não havendo diferença entre essas taxas
quando se considerou o grupo de crianças confirmadas e suspeitas para pneumonia.
Crianças na faixa etária de 36 a 47 meses formaram o grupo com maior risco de ter
pneumonia bacteriana (OR: 3.17 [1.29-7.88]). Entre os sorotipos encontrados, o
sorogrupo 6 (6A/6B) (17,3%) foi predominante, seguido dos sorotipos 14 (15,4%),
19F (10,6%), sorogrupo 15 (15B/15C) (9,6%), 23F (6,7%) e o sorotipo 19A (6,7%).
Os demais sorotipos e sorogrupos compreenderam 33,7%. O padrão de sorotipos foi
semelhante aqueles encontrados nos casos de meningite pneumocócica na cidade
de Salvador. Um total de 41 isolados (39,8%) apresentaram CIM ≥ 0,125 μg/mL para
penicilina e a resistência a SMX-TMP foi identificada em 69,2% dois isolados. A
tipagem por PFGE identificou 11 padrões eletroforéticos, sendo que a maioria dos
isolados do sorotipo 14 estavam relacionados a clones amplamente disseminados
entre os casos de doença pneumocócica (“A” e “GK”). Um total de 50,5% dos
isolados foram de sorotipos inclusos na vacina decavalente (PCV10) e considerando
os isolados não-susceptíveis à penicilina, esta representatividade foi de 90,2%. O
estudo ressalta a importância de um contínuo monitoramento do perfil de sorotipos
na colonização nasofaringeana por S. pneumoniae, no período pós-vacina e da
necessidade de busca de novos métodos de diagnóstico que otimizem a definição
da pneumonia.<br>Streptococcus pneumoniae is one of the most important bacterial pathogens of the
respiratory tract, causing invasive and noninvasive infections, leading to high rates of
morbidity and mortality, particularly among children under five years old. The
bacterium gains access to the host by colonizing the nasopharynx, which represents
an important reservoir for transmission of this pathogen in the community,
contributing to the horizontal spread of S. pneumoniae among individuals in a
population. In this study, we sought to characterize the profile of nasopharyngeal
colonization by S. pneumoniae in patients under five years of age with clinical
suspicion of pneumonia seeking medical care at the Unidade de Saúde de São
Marcos, District of Pau da Lima, Salvador, in 2009. A total of 205 swabs were
collected from children eligible for the study. The isolates of S. pneumoniae were
identified by classical methods and the determination of the serogroup / serotype was
performed using the technique of multiplex-PCR. The sensitivity to seven antibiotics
was tested by the microdilution broth method, and strains with MIC for penici≥lli n
0.125 mg/mL were considered non-susceptible. The PFGE technique was performed
for 26 strains corresponding to serotypes more frequent and associated with nonsusceptibility
to penicillin (serotypes 14, 19F and 23F). A total of 72 (35.1%) children
were diagnosed with pneumonia, 39 (54.2%) less than two years old. The overall
colonization rate was 50.2%, with no difference between those rates when
considering the children's group confirmed and suspected to pneumonia. Children
aged 36 to 47 months formed the group with higher risk for bacterial pneumonia (OR:
3.17 [1.29-7.88]). Among the serotypes, serogroup 6 (6A/6B) (17.3%) predominated,
followed by serotypes 14 (15.4%), 19F (10.6%), serogroup 15 (15B/15C) (9.6%), 23F
(6.7%) and serotype 19A (6.7%). The other serotypes and serogroups comprised
33.7%. The pattern of serotypes was similar to those found in cases of
pneumococcal meningitis in Salvador. A total of 41 isolates (39.8%) had MIC ≥ 0.125
mg / mL and resistance to TMP-SMX was identified in 69.2% of isolates. Molecular
typing identified 11 electrophoretic patterns, whereas most isolates of serotype 14
was associated with widespread clones among cases of pneumococcal disease ("A"
and "GK"). The 10-valent conjugate vaccine (PCV10) implemented in Brazil shows a
coverage of 50.5% from serotypes in the population and 90.2% for isolates not
susceptible to penicillin. The study underscores the importance of continued
monitoring of the prevalence of serotypes in nasopharyngeal colonization by S.
pneumoniae, in the post-vaccine era, and the need to search for new methods for
diagnosing pneumonia.
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Scholtz, Janet. "The serotypes and antimicrobial susceptibility patterns of streptococcus pneumoniae in the Cape Peninsula." Thesis, Cape Technikon, 2000. http://hdl.handle.net/20.500.11838/1464.
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Thesis (Masters Diploma(Technology))--Cape Technikon, Cape Town, 2000<br>Streptococcus pneumoniae (S.pneumoniae) infections are an important cause of
morbidity and mortality in adults and children worldwide. Mortality rates are highest
amongst the very young and the elderly. Streptococcus pneumoniae is the most
common form of community acquired bacterial pneumonia. Other diseases commonly
caused by Streptococcus pneumoniae include meningitis, pericarditis, bacteraemia and
septicaemia. Penicillin is today still consid3red the drug of choice when treating
pneumococcal infections. The emergence of resistant pneumococcal strains has made
it necessary to adapt antimicrobial regimens when treating pneumococcal infections.
Hansman (1967) reported the first penicillin resistant strain, which was isolated from a
woman in Australia in 1967. Since then penicillin and multi-resistant Streptococcus
pneumoniae strains have been observed worldwide, including South Africa.
Streptococcus pneumoniae infections may be caused by anyone of the 84 serotypes
recognized to date. The distribution of serotypes varies, depending on geographical
area, age and site of infection. High-level penicillin resistance and multiple resistant
Streptococcus pneumoniae strains have been recognised worldwide in a few
pneumococcal serotypes. Pneumococcal vaccines have been used since the seventies.
These capsular polysaccharide vaccines are generally recommended for at risk
population such as the elderly and immunocompromised patients. This vaccine is not
effective in children under 2 years old. The current vaccine in South Africa (Pneumovax,
MSD) consists of purified capsular polysaccharides of 23 pneumococcal serotypes.
Conjugated polysaccharide vaccines have been developed to overcome the problems
of efficacy in children < 2 years old. These vaccines consist of a capsular
polysaccharide linked to a protein carrier, which makes them immunogenic in infants.
Clinical trials of these vaccines are currently under way to demonstrate safety, efficacy
and immunogenicity.
Knowledge of serotype distribution and antimicrobial susceptibility patterns are
important in relation to the treatment of pneumococcal diseases and vaccination
programmes.
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Machado, Lais Del Prá Netto. "Pneumonia bacteriana adquirida na comunidade: avaliação clínico-epidemiológica e padronização de métodos moleculares para detecção de Mycoplasma pneumoniae, Haemophilus influenzae e Streptococcus pneumoniae." reponame:Repositório Institucional da UFSC, 2015. https://repositorio.ufsc.br/xmlui/handle/123456789/158899.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2015.<br>Made available in DSpace on 2016-02-09T03:17:04Z (GMT). No. of bitstreams: 1
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Previous issue date: 2015<br>A pneumonia pode ser causada por diversos microrganismos e classificada de forma abrangente, havendo poucos e frágeis estudos clínicos e epidemiológicos sobre pneumonias adquiridas na comunidade (PACs). Os patógenos mais frequentes nas PACs são Streptococcus pneumoniae e Haemophilus influenzae (em pneumonias típicas) e Mycoplasma pneumoniae (em pneumonias atípicas). Assim, o objetivo deste trabalho foi padronizar uma metodologia para detecção molecular dessas bactérias em amostras de orofaringe, avaliar sua prevalência e o perfil clínico-epidemiológico de pacientes com PAC em um hospital na cidade de Blumenau/SC. Para tanto, além da técnica de PCR padronizada in house, foram realizadas culturas de raspado de orofaringe e pesquisa de anticorpos específicos para detecção de M. pneumoniae. A reação de PCR realizada com os iniciadores desenhados neste estudo para M. pneumoniae apresentou sensibilidade 10x maior que a reação mais citada na literatura, e a sensibilidade das reações para S. pneumoniae e H. influenzae foi 0,1ng de DNA/reação. Dos 58 pacientes incluídos no estudo, H. influenzae e S. pneumoniae foram detectados respectivamente em 41,38% e 15,52% das amostras. M. pneumoniae não foi detectado em nenhuma amostra analisada por métodos de cultura, PCR e sorologia com anticorpos específicos IgM. Todavia não se exclui a circulação dessa bactéria na região devido à presença de anticorpos IgG específicos. A maioria dos pacientes com PAC avaliados apresentou idade =65 anos e pelo menos uma comorbidade. A maioria dos pacientes apresentou quatro ou mais sinais e sintomas, destes os mais prevalentes foram dispneia, tosse, secreção purulenta e crepitações. Evidenciou-se, neste estudo, a baixa aderência dos clínicos às Diretrizes Brasileiras para diagnóstico, estratificação e tratamento dos pacientes com suspeita de PAC, pois os exames complementares para diagnóstico e avaliação de risco dos casos e o antibiótico escolhido para grande parte dos pacientes não estava de acordo com a determinação das diretrizes. Sugere-se a replicação desta pesquisa, pois os resultados foram de encontro àqueles apresentados na literatura relacionada ao entendimento de PAC, acompanhamento dos ciclos epidêmicos de M. pneumoniae na região e conhecimento da real prevalência dos patógenos típicos, uma vez que o H. influenzae foi o patógeno mais detectado.<br><br>Abstract : Pneumonia can be caused by different microorganisms and classified through comprehensive forms, but there are few and fragile clinical and epidemiological studies of community-acquired pneumonia (CAPs). The most common pathogens in CAPs are Streptococcus pneumoniae and Haemophilus influenzae (in typical pneumonia) and Mycoplasma pneumoniae (in atypical pneumonia). Therefore, the aim of this study was to standardize a methodology for molecular detection of these bacteria in the oropharynx samples, and to evaluate their prevalence and the clinical and epidemiological profile of patients with CAP in a hospital in Blumenau/SC. Thus, besides the standard technique PCR in-house, oropharyngeal swab cultures and search for specific antibodies for detection of M. pneumoniae were performed. The PCR reaction performed with primers designed in this study for M. pneumoniae showed sensitivity greater than 10-fold the most cited in the literature reaction and the sensitivity of the reactions to S. pneumoniae and H. influenzae was 0.1 ng DNA / reaction. Out of the 58 patients included in the study, H. influenzae and S. pneumoniae were detected respectively in 41.38% and 15.52% of the samples. M. pneumoniae was not detected in any sample analyzed by culture methods, PCR and serology with IgM specific antibodies. Nevertheless it is not possible to exclude the circulation of this bacterium in the region due to the presence of specific IgG antibodies. Most CAP patients evaluated were 65 years or older and had at least one comorbidity. Most of the patients had four or more signs and symptoms, the most prevalent ones were dyspnea, cough, purulent secretion and crackles. It is evident in this study the low adherence of the practitioners to Brazilian Guidelines for the diagnosis, stratification and treatment of patients with suspected CAP, as the laboratory tests for diagnosis and case risk assessment and also the antibiotic selected for most patients were not determined according to the guidelines. Replication of this research is indicated for a better understanding of the CAP, support of epidemic cycles of M. pneumoniae in the region and knowledge of the real prevalence of the typical pathogens.
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Pratt, Stephanie Ann. "Immunoglobulin A1 protease of Streptococcus pneumoniae." Thesis, University of Leicester, 1988. http://hdl.handle.net/2381/35410.
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The aim of this project was to examine the Streptococcal IgA1 proteases, with particular interest on the Streptococcus pneumoniae enzyme. IgA1 protease of S. pneumoniae was identified and characterised. A non-reducing polyacrylamide gel system was employed to screen clinical isolates for IgA1 protease activity. Of 187 isolates tested 18% were found to be IgA1 protease negative, there was no correlation with the site of isolation of the organism and its ability to produce the enzyme. Attempts were made to clone the pneumococcal IgA1 protease gene using the cosmid pEMBLcos4, the plasmid vector pLG339 and the ? replacement vector ?EMB4. Libraries were screened for pneumolysin and IgA1 protease activity. Clones that expressed pneumolysin were identified by overlaying with sheep red blood cells. One haemolytic clone was not inhibited in the presence of cholesterol. Screening for IgA1 protease activity identified clones with IgA1 protease-ike activity but this activity was not stably expressed. Closer analysis of the libraries suggested that pneumococcal DNA was highly unstable when cloned into E. coil plasmid and cosmid vectors.
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Ho, Pak-leung, and 何柏良. "Emerging antimicrobial resistance in Streptococcus pneumoniae." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290999.
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Ibrahim, Yasser Musa. "Stress response proteins in Streptococcus pneumoniae." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412962.
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Ouennane, Siham. "Interactions phage-hôte chez Streptococcus pneumoniae." Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27790.
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Streptococcus pneumoniae est une bactérie à la fois commensale et pathogène opportuniste chez l’humain. Elle est responsable de nombreuses infections telles que la pneumonie, la méningite, l’otite moyenne et la sinusite. En maladie infectieuse, S. pneumoniae occupe une place importante en tant que l’une des principales causes de morbidité et de mortalité dans le monde. Elle est dotée de plusieurs capacités fascinantes, comme la compétence naturelle pour l’aider à résister aux antibiotiques et la grande diversité des sérotypes capsulaires pour contourner la vaccination. Puisque la résistance aux antibiotiques ne cesse de menacer l’efficacité des thérapies standards, la thérapie par phage est maintenant reconsidérée comme une des alternatives thérapeutiques. La réévaluation des phages fait renaitre l’espoir thérapeutique, mais sans élucider leur mécanisme d’interaction et décortiquer leur mystère cet espoir restera modeste. Ce projet de doctorat consiste à mieux comprendre les phages infectant S. pneumoniae et les interactions phage-hôte. Dans un premier temps, le potentiel des pneumophages à infecter Streptococcus mitis, une espèce phylogénétiquement proche de S. pneumoniae, a été mis en évidence. Deux pneumophages se sont avérés les premiers phages virulents capables d’infecter S. mitis, bactérie pathogène responsable d’endocardite. Les deux phages pouvaient non seulement se répliquer dans S. mitis mais également produisent des plages de lyses plus visibles. Ensuite, la comparaison du génome des phages a confirmé que le changement de l’hôte n’induit aucune variation aux génomes des phages testés. Cependant, plusieurs mutations ont été observées dans la séquence génomique du podophage sauvage et il a fait ensuite l’objet d’une nouvelle annotation. Dans un deuxième temps, l’étude des interactions phage-hôte chez S. pneumoniae a été approfondie. Pour ce faire, l’implication de plusieurs facteurs de l’hôte dans la réplication des pneumophages a été étudiée. Plusieurs gènes pneumococciques se sont avérés nécessaires ou impliqués pour assurer l'efficacité de la réplication des phages seuls ou en cocktail. D’un autre côté, en étudiant ces facteurs de l’hôte, des gènes/ protéines potentiellement essentiels à la viabilité de S. pneumoniae ont été identifiés. Cette étude a aussi permis d’identifier de nouvelles cibles thérapeutiques et donne un nouvel aperçu du réseau complexe des interactions phage-hôte.<br>Streptococcus pneumoniae is a commensal and opportunistic pathogen bacterium, exclusively found in humans. It is the main agent of many infections such as pneumonia, meningitis, otitis media and sinusitis. S. pneumoniae infections are a major cause of morbidity and mortality worldwide. S. pneumoniae has several fascinating abilities, such as natural competence to facilitate the acquisition of antibiotic resistance genes and diversity of capsular serotypes to circumvent the vaccination. The rise of antibiotic resistant bacteria continues to threaten the effectiveness of standard therapies and as such phage therapy is now reconsidered as a therapeutic alternative. The reevaluation of phages as therapeutic agents must go through a better understanding of phage-bacterium interactions. This PhD thesis aims to better understand S. pneumoniae virulent phages and phage-host interactions. First, the ability of pneumophages to infect Streptococcus mitis, a species phylogenetically related to S. pneumoniae, was demonstrated. The pneumophages are the first two virulent phages able to infect this pathogenic bacterium, the common cause of bacterial endocarditis. Both pneumophages could not only replicate in S. mitis but also produced more visible plaques on this host. The comparison of the genomes of each phage grown on both hosts produced identical nucleotide sequences, confirming that S. mitis as a host does not induce any nucleotide variation. However, the genomic sequence of wild-type podophage was different than the previously reported sequence and it was the subject of a new annotation. In addition, S. pneumoniae phage-host interactions were investigated. The involvement of several host factors in replication of both pneumophages was observed. Indeed, several pneumococcal genes were found to be necessary or involved to ensure efficient phage replication. Moreover, the study of these host factors has led to the identification of new genes that appear to be essential for viability and normal growth of S. pneumoniae. This project led to identify new potential therapeutic targets and provided new insight into the complex network of phage-host interactions.
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Carvalho, Ricardo Jorge da Silva. "Revisiting molecular diagnostics of Streptococcus pneumoniae." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16115.
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Mestrado em Biologia Molecular e Celular<br>Streptococcus pneumoniae is a human pathobiont that colonizes the nasopharynx. S. pneumoniae is responsible for causing non-invasive and invasive disease such as otitis, pneumonia, meningitis, and sepsis, being a leading cause of infectious diseases worldwide. Due to similarities with closely related species sharing the same niche, it may be a challenge to correctly distinguish S. pneumoniae from its relatives when using only non-culture based methods such as real time PCR (qPCR). In 2007, a molecular method targeting the major autolysin (lytA) of S. pneumoniae by a qPCR assay was proposed by Carvalho and collaborators to identify pneumococcus. Since then, this method has been widely used worldwide. In 2013, the gene encoding for the ABC iron transporter lipoprotein PiaA, was proposed by Trzcinzki and collaborators to be used in parallel with the lytA qPCR assay. However, the presence of lytA gene homologues has been described in closely related species such as S. pseudopneumoniae and S. mitis and the presence of piaA gene is not ubiquitous between S. pneumoniae. The hyaluronate lyase gene (hylA) has been described to be ubiquitous in S. pneumoniae. This gene has not been used so far as a target for the identification of S. pneumoniae. The aims of our study were to evaluate the specificity, sensitivity, positive predicted value (PPV) and negative predicted value (NPV) of the lytA and piaA qPCR methods; design and implement a new assay targeting the hylA gene and evaluate the same parameters above described; analyze the assays independently and the possible combinations to access what is the best approach using qPCR to identify S. pneumoniae. A total of 278 previously characterized strains were tested: 61 S. pseudopneumoniae, 37 Viridans group strains, 30 type strains from other streptococcal species and 150 S. pneumoniae strains. The collection included both carriage and disease isolates. By Mulilocus Sequence Analysis (MLSA) we confirmed that strains of S. pseudopneumoniae could be misidentified as S. pneumoniae when lytA qPCR assay is used. The results showed that as a single target, lytA had the best combination of specificity, sensitivity, PPV and NPV being, 98.5%, 100.0%, 98.7% and 100.0% respectively. The combination of targets with the best values of specificity, sensibility, PPV and NPV were lytA and piaA, with 100.0%, 93.3%, 97.9% and 92.6%, respectively. Nonetheless by MLSA we confirmed that strains of S. pseudopneumoniae could be misidentified as S. pneumoniae and some capsulated (23F, 6B and 11A) and non-capsulated S. pneumoniae were not Identified using this assay. The hylA gene as a single target had the lowest PPV. Nonetheless it was capable to correctly identify all S. pneumoniae.<br>Streptococcus pneumoniae é uma bactéria patogénica que coloniza a nasofaringe humana. S. pneumoniae é responsável por causar doenças, tanto invasivas como não invasivas como: otite, pneumonia, meningite e sepsis, continuando a ser uma das principais causas de doenças infecciosas a nível mundial. Devido a semelhanças com espécies que lhe são estreitamente relacionadas, e que compartilham o mesmo nicho ecológico, pode ser um desafio identificar corretamente S. pneumoniae aplicando apenas técnicas não dependentes do passo de cultura bacteriana como a técnica de PCR em tempo real (qPCR). Em 2007, um método molecular para identificação de S. pneumoniae baseado num qPCR e tendo como alvo o gene da autolisina principal (lytA) de S. pneumoniae foi proposto por Carvalho e seus colaboradores. Desde então, este tem sido usado de uma forma sistemática por vários grupos. Em 2013, foi proposto por Trzcinszki e seus colaboradores o uso da lipoproteína ABC transportadora de ferro PiaA como alvo num qPCR. O piaA qPCR foi usado em paralelo com o lytA qPCR. Contudo, a presença de genes homólogos de lytA foi descrita em espécies filogeneticamente próximas, como S. pseudopneumoniae e S. mitis, e a presença do gene piaA não é ubíquo entre S. pneumoniae. O gene da proteína hyaluronato lyase (hylA) é descrito como sendo ubíquo a todas as estirpes de S. Pneumoniae. Este gene ainda não foi usado até ao momento como alvo para a identificação de S. pneumoniae. Assim o objectivo do nosso estudo foi a avaliação da especificidade, sensibilidade, valor positivo preditivo (VPP) e valor negativo preditivo (VNP) do método lytA e piaA qPCR; construção de hylA qPCR avaliando os mesmos parâmetros acima referidos; analise dos ensaios de uma forma independente e em conjunto, para poder retirar conclusões sobre qual o melhor gene alvo, ou alvos, a usar na identificação de S. pneumoniae. Foram testadas um total de 278 estirpes anteriormente caracterizadas: 61 S. pseudopneumoniae, 37 estirpes do grupo Viridans, 30 estirpes referência de outras espécies de Streptococcus e 150 estirpes de S. pneumoniae. A coleção usada incluía tanto estirpes obtidas em colonização como estirpes obtidas em doença. Através do método Multilocus sequence analysis (MLSA) verificámos que estirpes de S. pseudopneumoniae podem ser incorretamente identificadas como S. pneumoniae quando é utilizado o lytA qPCR. Ainda assim, os resultados mostraram que como alvo único, o gene lytA apresenta a melhor combinação de valores de especificidade, a sensibilidade, VPP e VNP sendo, respetivamente, 98.5%, 100.0%, 98.7% e 100.0%. A combinação de genes com a melhor combinação de valores de especificidade, sensibilidade, VPP e VNP foi lytA e piaA, com 100.0%, 93.3%, 97.9% e 92.6%, respetivamente. De realçar que pelo método MLSA verificámos que estirpes de S. pseudopneumoniae podem ser incorretamente identificadas como S. pneumoniae e algumas estirpes capsuladas (23F, 6B e 11A) e não-capsuladas de S. pneumoniae não são identificadas quando usada esta combinação de genes. O gene hylA como alvo único apresentou o valor de PPV mais baixo, todavia identificou corretamente todos os S. pneumoniae.
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Chewapreecha, Kamolchanok. "Evolution of Streptococcus pneumoniae during carriage." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708595.
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Ho, Pak-leung. "Emerging antimicrobial resistance in Streptococcus pneumoniae." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290999.
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Burman, Lars Å. "Streptococcus pneumoniae : epidemiological, clinical and serological studies." Doctoral thesis, Umeå universitet, Infektionssjukdomar, 1993. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-102563.
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A retrospective study of invasive pneumococcal disease in patients from Greater Göteborg in 1964- 1980 identified 125 cases of meningitis, 305 of pneumonia, 61 of septicemia with unknown focus, and 17 with other manifestations, all verified by cultures from normally sterile body fluids. The incidence was several times higher in infants and in the elderly than in any other age-group. A wide variety of underlying conditions were present in 23% of the infants, 34% of the children, and 81% of the adults. In adults alcoholism was known in one third of the cases. The case fatality rate was 24% among patients with underlying conditions and 9% among previously healthy individuals. The case fatality rate was 50% in patients with hospital-acquired infection. Twohundred-fifteen pneumococcal strains, isolated from blood or CSF from 1971 to 1983 at the laboratories of clinical bacteriology of Göteborg, Malmö, and Umeå were serotyped by coagglutination (COA). Of all isolates, 89% belonged to serotypes represented in the 23-valent vaccine. In a separate study COA was compared with counterimmunoelectrophoresis (CIE). COA was found to have several advantages; rapidity, lower cost, and ability to disclose serotypes with neutral charge, which constituted 19% of all strains. In a prospective study the etiology was determined in 196 hospitalized patients with pneumonia, most of them community-acquired. Culture of specimens from blood, transtracheal aspirate (TTA), sputum, and nasopharynx, assays of antigen in sputum, urine, and TTA, and assays of pneumococcal antibodies to capsular polysaccharide, C-polysaccharide, and pneumolysin in paired sera were performed. The etiology was established in 64% of the patients. Streptococcus pneumoniae was the most common agent (32%). In a serological study of patients with pneumococcal infection, diagnosed by culture of CSF, TTA, or blood, IgG antibodies against C-polysaccharide and pneumolysin were determined by ELISA. The diagnostic sensitivity was only 51% and 60%, respectively. In conclusion, invasive pneumococcal disease is strongly overrepresented at tender and high age and in patients with concomitant conditions, notably alcoholism. S. pneumoniae remains a predominant causative agent of community-acquired pneumonia in adults needing hospitalization. Due to the low sensitivity and/or specificity of individual microbiological techniques, a combined use of several techniques is necessary when trying to assess the relative importance of pneumococci and other agents in pneumonia. Extended use of the currently available pneumococcal vaccine and development of improved pneumococcal vaccines seem highly warranted.<br><p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 5 uppsatser.</p><br>digitalisering@umu.se
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Ekdahl, Karl. "Immunological aspects on pneumococcal infections with special reference to bacteremic pneumococcal infections and recurrent pneumonia /." Lund : Dept. of Infectious Diseases, University of Lund, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39177549.html.
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Morona, Judy Kay. "Characterisation of the capsular polysaccharide biosynthesis loci of streptococcus pneumoniae serogroup 19 /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phm8678.pdf.
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CARRARO, MONICA. "Identification of infection biomarkers in a murine model of pneumonia by Streptococcus pneumoniae." Doctoral thesis, Università di Siena, 2018. http://hdl.handle.net/11365/1037742.
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Streptococcus pneumoniae infections remain a public health problem despite the availability of vaccines. In order to study alternative preventive strategies it is essential to have a reliable animal model of the infection. To date, the majority of vaccine efficacy evaluation studies still rely on direct read-outs such as the survival rate after challenge and the CFU counts in blood and in the lungs. A murine model of lung infection was developed in which animal death was not the endpoint: clinical parameters, cellular lung infiltrate and systemic immune response were evaluated in (i) infected mice, (ii) vaccinated mice, and (iii) vaccinated and challenged mice. All these parameters were used to identify biomarkers of sublethal pneumonia and protection following vaccination with the pneumococcal conjugate vaccine.
Female C57BL/6 mice were infected with different doses of S. pneumoniae strain TIGR4, the dose of 1.6 x 107 CFUs was capable to induce measurable signs of the disease with a 100% survival and was therefore used for subsequent experiments. Histological examination and flow cytometry analysis of the lung tissue were performed at different time-points after bacterial inoculation. Data revealed that absolute numbers of the cell populations evaluated through flow cytometry were significantly different 7 days after the infection from those of uninfected mice, and histological evaluation of the lungs at this time-point also revealed the presence of leukocyte infiltrate. The presence of the infiltrate represented a biomarker of infection. When mice were vaccinated prior to pneumococcal challenge, they showed no weight loss and a mild infiltrate in the lungs. The absence of the infiltrate in relation with mild clinical signs and a good humoral response defined the protected phenotype.
The type of immune response mounting following interaction of the immune system with S. pneumoniae was evaluated using mice splenocytes re-stimulated in vitro with inactivated TIGR4. The production of 23 cytokines was measured, revealing that splenocytes started to react to in vitro re-stimulation at 4 days after infection and peaking 7 days after infection. A predominant production of IFN-γ and IL-17 was observed in infected mice, while this profile was skewed to Th2 characteristic cytokines such as IL-4 and IL-5 when mice had received the vaccine. These features, together with cellular infiltrates observed in the lungs, can be considered biomarkers of protection that could be used to study the protection induced by a vaccine candidate using parameters other than the survival rates and the CFU counts.
We identified measurable and reliable biomarkers of pneumococcal pneumonia that could be investigated in vaccine efficacy studies and could become tools to develop new immunization strategies against S. pneumoniae.
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Gingles, Neill. "Murine mechanisms of resistance to Streptococcus pneumoniae." Thesis, University of Leicester, 2000. http://hdl.handle.net/2381/29811.
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The aim of this thesis was to investigate the basis of genetic resistance or susceptibility to infection with S. pneumoniae using a mouse model of bronchopneumonia. To this end, a panel of strains of inbred mice was intranasally infected with S. pneumoniae type 2 strain (D39), and type 3 (GB05). BALB/c mice were resistant and CBA/Ca were susceptible to infection, particularly with D39 pneumococci. To analyse the genetic inheritance, filial generations (F1 mice and F2 mice) were produced from intercross breeding these two strains and subsequently challenged with D39 pneumococci. Further investigation of the parental strains using D39 pneumococci revealed that BALB/c mice, unlike CBA/Ca mice, were able to prevent proliferation of pneumococci in lungs and blood. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca, in contrast to BALB/c. Analysis of the cellular response to infection provided data to show that BALB/c mice were able to recruit more leukocytes into the lungs than CBA/Ca mice, following infection. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 hours post-infection. Histological studies reflected the cellular recruitment data. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice and there was a greater cellular infiltration into the lung tissue of BALB/c mice, at the earlier time points. Data presented in this thesis suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils. Continuing analysis will reveal possible additional loci and further define the genes involved in the susceptibility or resistance to pneumcoccal disease.
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Gillespie, S. H. "Species specific diagnosis of Streptococcus pneumoniae infection." Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261768.
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Yang, Yiping. "Characterisation of extracellular proteases of Streptococcus pneumoniae." Thesis, University of Sunderland, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402832.
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Ali, Farzana. "Streptococcus pneumoniae induced monocyte-derived-macrophage apoptosis." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397500.
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Perry, Frances. "Oxidative responses of neutrophils to Streptococcus pneumoniae." Thesis, University of Bristol, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335509.
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Cohen, J. M. "Colonisation-induced protection against Streptococcus pneumoniae disease." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1124359/.
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Streptococus pneumoniae is an important human pathogen, yet in most individuals it establishes only transient nasopharyngeal colonisation without causing disease. Using murine models, this thesis explores the hypothesis that colonisation induces acquired immune responses which protect against subsequent pneumonia. Colonisation models with wild-type (WT) and mutant S. pneumoniae were established in outbred CD1 mice. Mutants lacked either capsule or lipoproteins, or were auxotrophs unable to replicate in vivo. WT colonisation protected against subsequent pneumonia. Mutants were cleared more rapidly than WT, were not immunogenic and did not protect. When the auxotroph was supplemented, colonisation, immunogenicity and protection were improved, suggesting duration of a colonisation event is an important factor in determining immunogenicity. This may be one factor explaining the poor immunogenicity of the other mutants. The mechanism by which previous colonisation protected against subsequent lethal pneumonia was then defined in a series of studies in inbred CBA/Ca mice. Colonisation induced both mucosal and systemic antibody responses to bacterial surface antigens but not capsule. There was also evidence of more robust cytokine production during subsequent pneumonia, including systemic and mucosal IL-17 responses dependant on the presence of CD4-cells. Protection was primarily against systemic invasion following pneumonia. Passive transfer studies and experiments using genetically modified mice demonstrated that systemic antibody was both necessary and sufficient to protect, and in vitro and in vivo models showed this to be via opsonophagocytosis and bloodstream clearance of bacteria. Antigenic protein targets of protective serum were defined using Western blotting and multiplex bead immunoassay techniques. Overall this thesis demonstrates that nasopharyngeal colonisation can protect against lethal pneumonia in mice via opsonophagocytic antibody against surface proteins thus preventing bacteraemia.
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Abrahams, Katherine Anne. "The enzymology of Streptococcus pneumoniae peptidoglycan polymerisation." Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/53797/.
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Bacterial cell survival depends on intact peptidoglycan, an extensive cell wall polymer of alternating N-acetylglucosamine and N-acetylmuramic acid residues, cross-linked by short peptides. Peptidoglycan biosynthesis is a viable and validated antimicrobial target; the intracellular, membrane-bound and extracellular synthetic stages provide a multitude of enzymes for interception with inhibitors. The ultimate phase of peptidoglycan biosynthesis occurs on the extracellular face of the cytoplasmic membrane and involves the polymerisation of Lipid II (the monomeric peptidoglycan precursor) by the transglycosylase and transpeptidase activities of the Penicillin-Binding Proteins (PBPs). The work presented in this thesis primarily focused on the biochemical characterisation of the integral membrane proteins Streptococcus pneumoniae PBP1a, PBP2b and PBP2x. These enzymes are clinically relevant; they are essential targets of !-lactam antibiotics and also mediate resistance against this important antimicrobial class. Full-length and truncated forms of the PBPs were cloned, expressed and purified to high levels. Two novel spectrophotometric assays were designed and developed to study the enzymology of the individual transglycosylase and transpeptidase activities of the PBPs with their natural substrate, Lipid II. Preliminary kinetic characterisations of the bifunctional PBP1a transglycosylase activity were performed and assay conditions were optimised to recreate an in vivo environment. PBP1a active site mutants revealed that transglycosylase activity was elevated in the absence of a functional transpeptidase domain. PBP1a and PBP2x exhibited transpeptidase activity with an apparent substrate preference for glycan polymers over Lipid II. PBP2x transpeptidase activity was not detected. The recorded rates of PBP activity were insufficient to support bacterial cell integrity, highlighting a gap in the understanding of PBP requirements. Finally, the PBPs were subjected to crystallisation trials for structural characterisations. This work provides an excellent foundation for the analysis and elucidation of PBP specificities. Future information attained could contribute to the design of novel inhibitors, alleviating the global threat of antibiotic resistance.
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Herbert, Jenny. "Genetic regulation of virulence in Streptococcus pneumoniae." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/4204/.
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S.pneumoniae is the leading cause of bacterial pneumonia and meningitis. Pneumonia alone has been estimated to kill more children under the age of five than that caused by AIDS, malaria and tuberculosis combined. The current vaccines which are used to prevent pneumococcal infection only protect against a small number of the 90+ serotypes currently identified. Current issues which may prevent the long term use of these vaccines is capsular switching, a phenomenon observed where some strains are able to escape the vaccine through switching their capsule genes. Further serotype replacement has been shown to occur since the introduction of the PCV7 vaccine, where serotypes not protected against by the vaccine have caused a higher incidence of invasive pneumococcal disease compared to the pre vaccine era. One strategy to avoid this is via the use of a multi-component protein based vaccine which is serotype independent. The pneumococcus is normally found as a harmless commensal yet can also cause invasive disease as stated above, the pneumococcus is also the leading cause of otitis media. The ability for the pathogen to occupy a number of different niches and evade host defences is attributed to its large cache of virulence factors, including numerous cell surface adhesins. The ability of the bacteria to regulate genes required for adaptation to a specified niche is vital for survival. In this study a number of signalling systems that are able to modulate gene expression (specifically virulence factors) to facilitate adaptation to varying environmental conditions are assessed to determine the genes they regulate. Further key environmental signals are evaluated to determine the effect they have on regulation of important cell surface adhesins. The main systems used to modulate global expression changes are two-component signal transduction systems (TCS). 13 TCS and one orphan response regulator are encoded in the pneumococcal genome. Little information is available with regards to the importance of each system, whether each system regulates its own separate collection of genes and the extent to which cross regulation may occur between these systems. This study used whole genome expression analysis data obtained through microarray analysis of single and double TCS mutants to assess the potential cross regulation of two chosen systems. A number of the systems have also been shown to regulate the same islet, which encodes a pilus. Measuring expression of the islet itself enabled the role of the systems shown to regulate the islet to be assessed for potential interactions between the systems and whether a hierarchy exists. The pneumococcus is highly genetically variable due to its ability to become naturally competent, taking up DNA from the environment and recombining it into its genomic DNA to aid genetic variation and survival. The new era of whole genome sequencing has begun to shed light on just how variable this pathogen is. Although a number of TCS have been shown to regulate pilus expression, with the use of whole genome sequencing of two closely related strains (one contains reduced pili expression levels) a number of other factors have also been identified which have been shown to alter pilus expression, this includes a serine/ threonine protein kinase, pyruvate oxidase and lactate oxidase. Further the pneumococcus has been shown to respond to exogenously added hydrogen peroxide which increases pilus expression levels. Levels of hydrogen peroxide may act as a key environmental cue to signal to the bacterium that they are present in the nasopharynx and require increased levels of cell surface adhesins.
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Noori, Muhammad Yahya. "Genetic variation and virulence of Streptococcus pneumoniae." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/4440/.
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Streptococcus pneumoniae or pneumococcus is included among major human pathogens and is responsible for a number of diseases including life-threatening conditions such as pneumonia, meningitis and sepsis. Though pneumococcal vaccines are available, they provide limited coverage against infections as pneumococcus shows extensive variation, which also allows escape from vaccines and antibiotic resistance. It is armed with several virulence factors including capsule, surface proteins, enzymes and toxins, which are variably expressed and altogether determine pneumococcal virulence. The aim of this project was to study pneumococcal genetic variation and its effect on virulence, with a focus on pneumococcal capsule, which is considered the major determinant of virulence and is involved in interaction with host immune system. It is the target for current vaccines and at least 93 pneumococcal serotypes are known, which differ in pathogenicity. To study the effect of capsule on the pneumococcal virulence, capsule-switch mutants were constructed in three genetic backgrounds; TIGR4 (serotype 4, virulent), 403 (serotype 4, avirulent) and D39 (serotype 2, virulent) and were studied for variation in their in vivo and in vitro characteristics. These mutants were compared with their parent strains and other mutants for effects of capsule switching on their growth, formation of capsular polysaccharide, capsular thickness, chain formation and virulence in murine models of infection using MF1 mice. Significant differences were observed in behaviour of parent and mutant strains. To develop a broader insight into pneumococcal virulence, avirulent derivative of strain TIGR4, 403 was genome sequenced and compared with TIGR4 for genetic mutations. To study differences in gene expression both the strains were also compared using microarrays. Genome analysis revealed only few mutations in strain 403 but microarray experiments showed 288 genes to be expressed differently in strain 403. Strain 403 was also tested as live attenuated vaccine to see if it could provide protection against the same and different serotypes, as it can be used as a vehicle for delivery of different polysaccharides to the host body along with the whole set of pneumococcal antigenome. Vaccine trials of 403 were not very fruitful as it failed to provide any protection through intranasal route though partial protection was observed in mice vaccinated intraperitoneally with significant differences in levels of bacteraemia, survival, weight and temperature losses on challenging with homologous strain.
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Pavao, Aiden. "Modeling the metabolic diversity of Streptococcus pneumoniae." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:109024.
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Thesis advisor: Tim van Opijnen<br>Each year, the opportunistic pathogen Streptococcus pneumoniae causes millions of illnesses and nearly 300,000 deaths worldwide. Despite widespread vaccination campaigns, S. pneumoniae persists as a public health risk in large part to its high genomic diversity. In previous work, our group has shown that functional pathways, including stress response to antibiotics, are not necessarily conserved between pneumococcal strains. Thus, a holistic pangenome view of S. pneumoniae is a promising avenue to gain understanding of the species and to inform clinical treatment methods. Our group has selected 36 strains, covering 78% of known pneumococcal genetic diversity, for S. pneumoniae pangenome studies. We have previously constructed transposon libraries and performed Tn-seq for 22 of these strains in both in vitro and in vivo conditions. From these studies, our group has constructed pangenome profiles of genes essential for reproduction in culture conditions, infection in a mouse model, and attachment in a human nasopharyngeal epithelial cell line. In this study, we develop and execute a pipeline to construct iSP20, a set of in silico metabolic models for 34 S. pneumoniae strains. We employ these models to predict nutrient and metabolic gene essentiality on both the strain and pangenome level, demonstrating that key patterns in the strains’ essentialomes translate to a metabolic context. Additionally, we perform a functional analysis of the metabolic models, revealing a highly connected metabolic genome and essentialome. We uncover differences in the in vitro and in silico core essentialomes and identify potential sources of discrepancy between the two datasets. Overall, this work demonstrates the utility of strain-specific metabolic models in pangenome essentiality studies and provides enhanced understanding of metabolism in S. pneumoniae<br>Thesis (BS) — Boston College, 2020<br>Submitted to: Boston College. College of Arts and Sciences<br>Discipline: Departmental Honors<br>Discipline: Biology
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Malak, H. "Pneumolysin-macrophage interactions in Streptococcus pneumoniae infection." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3001781/.
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Alsharif, Sultan M. M. "Stress response and pathogenicity in Streptococcus pneumoniae." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5231/.
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The pathogen Streptococcus pneumoniae encounters different levels of oxygen during the infection cycle including colonisation, pneumonia, bateraemia and meningitis. These different anatomical niches require high levels of genome changes to sense and respond to those external environmental stimuli. The bacterial gene expression is known to be affected by oxygen, and it must react properly for survival and for developing invasive pneumococcal desiseases (IPDs). Microarray techniques have allowed scanning the whole pneumococcal genome during growth in different tensions of oxygen mimicking in vivo conditions. It was found that oxygenated growth conditions have significantly elevated several key virulence genes. This was further confirmed with qRT-PCR for a selection of genes implicated in pathogenicity. Moreover, post-transcriptional stages have been also investigated such as protein production, biofilm formation, biological activities and adherence assays for several virulence factors performed under the effect of presence or absence of oxygen. The data illustrate that 420 out of 2,236 genes (17 % of the entire TIGR4 genome) were differentially expressed in the presence of oxygen compared to its absence. 262 genes (11 %) were over-expressed when pneumococci were grown in oxygenated conditions relative to transcriptional profile in anaerobic growth conditions, indicating the magnitude of roles played by oxygen on pneumococcal gene expression. Anaerobic growth of TIGR4 showed down-regulation of 158 genes (7 %). Oxygen modulates induction of ply, pspC and other seven genes involved in pili structuring subunits (rlrA, rrgA, rrgB and rrgC) and assembling enzymes (srtB, srtC and srtD). This may suggest that the pneumococcal population grown under atmospheric environment is equipped with greater capability to progress IPDs compared to anaerobically grown bacteria. In addition to this, pneumococcal adhesion in vitro for TIGR4 grown in oxygenated or anaerobic growth conditions revealed a significant increase in those grown in oxygenated growth conditions, indicating that oxygen may play a key role in bacterial-host attachment. Interestingly, ablation of pspC has resulted in similar adhesion percentages of TIGR4 grown under both conditions, oxygenated and anaerobic. Furthermore, several genes involved in metabolism were up-regulated in oxygenated environment, particularly transporters, which are considered highly important for a bacterium that lacks an electron transport chain, catalase and tricarboxylic acid. Additionally, the results showed phenotypic characterisation and changes in cells morphology from pneumococcal growth curves for several strainswith different genome backgrounds grown under different levels of oxygen concentrations. Further investigation of the pathogen biology revealed differences in pneumolysin production and activity. These findings highlight that virulence genes expression is induced once the micro-organism is exposed to oxygenated environment, and data analysis has demonstrated potential links between pneumococcal metabolism and their ability to cause diseases.
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Inverarity, Donald James. "Genomic diversity in naturally transformable Streptococcus pneumoniae." Thesis, Connect to e-thesis, 2009. http://theses.gla.ac.uk/901/.
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Thesis (Ph.D.) - University of Glasgow, 2009.<br>Ph.D. thesis submitted to Faculty of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, 2009. Includes bibliographical references. Print version also available.
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Østergaard, Andersen Christian. "Streptococcus pneumoniae meningitis : clinical and experimental studies /." KøbenhavnLægeforeningens Forlag : Lægeforeningens Forlag, 2007. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=015627763&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Coffey, Tracey Jean. "Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae." Thesis, University of Sussex, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357230.
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Halle, Annett. "Streptococcus pneumoniae induziert Apoptose in zerebralen Endothelzellen." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15193.
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Die bakterielle Meningitis ist trotz der Anwendung modernster Antibiotika mit einer hohen Letalität und neurologischen Spätkomplikationen verbunden. Ein entscheidendes Ereignis ist dabei der Zusammenbruch der Blut-Hirn-Schranke (BHS). Die genauen Mechanismen, die zu ihrer Schädigung führen, sind bis heute unklar. In dieser Arbeit wurde untersucht, ob lebende Pneumokokken in einem Zellkulturmodell der BHS zu einer apoptotischen Zellschädigung von zerebralen Endothelzellen, als wichtigstem zellulären Bestandteil der BHS, führen und damit zu ihrer strukturellen Schädigung beitragen. Mittels verschiedener Detektionsmethoden (TUNEL, Fluoreszenzmikroskopie, Elektronenmikroskopie) konnte nachgewiesen werden, daß Streptococcus pneumoniae zu einem apoptotischen endothelialen Zelltod führt. Eine Beteiligung von Caspasen konnte weder mit direkter Aktivitätsmessung noch mittels Inhibitionsexperimenten oder dem Nachweis von Caspase-spezifischen Substraten gezeigt werden. Insgesamt sind die Morphologie der Zellkerne und die spezifische Degradation der endothelialen DNS hinweisend für einen Apoptosis-Inducing-Factor-vermittelten Zelltod ohne Caspasenbeteiligung. Diese Form des Zelltodes ist bereits in anderen Zellmodellen, bisher jedoch nicht bei zerebralen Endothelzellen beschrieben worden. Auf Seiten des Bakteriums konnten Wasserstoffperoxid und Pneumolysin als Auslöser der Apoptose identifiziert werden. Die zytotoxische Potenz des Pneumolysins ist dabei an dessen Poren-formende Aktivität gebunden. Die Ergebnisse sind von potentieller klinischer Relevanz, da es bei einer Bakteriämie und während der Invasion der Pneumokokken in das ZNS zu einem direkten Kontakt zwischen Bakterien und zerebralen Endothelzellen kommt und sich daraus eine Möglichkeit zur Entwicklung adjuvanter Therapien ergeben könnte.<br>Despite sufficient antibiotic treatment, pneumococcal meningitis has remained a disease associated with high mortality and neurological sequelae. The disruption of the blood brain barrier (BBB) is regarded a key event in the initial phase of pneumococcal meningitis. However, the exact molecular mechanisms involved in this process are still unknown. The aim of this study was to determine if living pneumococci are able to induce apoptosis in cerebral endothelial cells - the main cellular component of BBB - and therefore might contribute to its damage. Using several different detection methods (TUNEL, fluorescence and electron microscopy), induction of apoptotic cell death of endothelial cells by pneumococci could be verified. An accompanying activation of caspases was not detectable, despite the use of specific detection techniques such as inhibition experiments, direct enzyme measurements and detection of caspase-specific protein cleavage. These results as well as the specific nuclear morphology and degradation of endothelial DNA suggest an involvement of the mitochondrial protein Apoptosis inducing factor (AIF). This is the first time this specific form of apoptotic, AIF-driven cell death has been described to be engaged in endothelial cells. On the part of the bacterium, pneumolysin and hydrogen peroxide were identified as the two main inducers of apoptosis. The cytotoxic potency of pneumolysin is related to its pore-forming activity. These results are of clinical relevance since pneumococci are known to reside in close proximity to cerebral endothelial cells during bacteriemia and their entry into the CNS. These findings could contribute to the development of adjuvant treatment of bacterial meningitis.
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Lock, Robert Arthur. "Studies on virulence proteins of Streptococcus Pneumoniae /." Title page, summary and table of contents only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09phl813.pdf.
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Leite, Ilaiáli Souza. "Inativação de Streptococcus pneumoniae por terapia fotodinâmica infravermelha com indocianina verde e sua interação com macrófagos RAW 264.7." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-17092015-110348/.
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As infecções do trato respiratório inferior lideram entre as principais causas de morbidade e mortalidade no mundo. Um dos grandes problemas associados ao tratamento das infecções do sistema respiratório, como as pneumonias, advém da crescente resistência aos mais modernos antibióticos adquirida pelos microrganismos. A terapia fotodinâmica, uma técnica baseada na interação da luz com uma substância fotoativa para causar dano oxidativo a células, tem se destacado como uma interessante alternativa para diversas doenças como diferentes tipos de câncer e infecções. Neste trabalho foi realizada, com experimentos in vitro, uma prova de princípio da possibilidade de inativar, com um protocolo eficiente e seguro, uma das bactérias mais comumente encontradas em quadros de pneumonia, a Streptococcus pneumoniae, com terapia fotodinâmica infravermelha mediada pela indocianina verde. Duas fontes de luz, uma a base de lasers emitindo 780 nm e outra construída com LEDs emitindo 850 nm, foram comparadas para avaliar sua eficiência. Experimentos com a bactéria foram realizados para determinação dos melhores parâmetros de inativação microbiana. Em seguida, ensaios de citotoxicidade foram feitos com macrófagos RAW 264.7 com o intuito de averiguar se as condições microbicidas não apresentavam atividade tóxica para células fagocitárias do sistema imune. Foi possível delinear os parâmetros de concentração de indocianina, tempo de incubação e dose de luz que apresentassem atividade microbicida e que não fossem tóxicas para as células. A interação da terapia fotodinâmica com a ação fagocitária dos macrófagos sobre as bactérias foi avaliada pelo estabelecimento de co-cultura dessas espécies. Concluiu-se que, utilizando-se LEDs de 850 nm fornecendo uma dose de luz de 10 J/cm2 as amostras contendo indocianina verde 5μM, é possível inativar S. pneumoniae de modo eficiente e auxiliar a ação fagocitária de macrófagos.<br>The lower respiratory tract infections lead among the main causes of morbidity and mortality worldwide. A major problem associated with respiratory tract infections, e.g. pneumonia, stems from from the increasingly resistance to most modern antibiotics developed by microorganisms. Photodynamic therapy, a technique based on the interaction of light and a photoactive substance to cause oxidative damage to cells, has emerged as an attractive alternative for several diseases such as different kinds of cancer and infections. In this work, with in vitro experiments, we accomplished a proof of concept for the possibility of inactivating, with an efficient and secure protocol, one of the most commonly found bacteria in pneumonia cases, Streptococcus pneumoniae, with infrared photodynamic therapy mediated by indocyanine green. Two light sources, one based on 780 nm lasers and the other built with 850 nm LEDs, were compared to evaluate their efficiency. Experiments with bacteria determined the best parameters microbial inactivation. Then, cytotoxicity assays with RAW 264.7 macrophages analyzed if the microbicidal parameters had toxic effects on immune cells. It was possible to delineate the indocyanine concentration parameters, incubation time and dose of light to obtain microbicidal results that weren´t toxic to the cells. Interaction of photodynamic therapy with the phagocytic action of macrophages on the bacteria was assessed by establishing a co-culture with these species. We concluded that, using 850 nm LEDs providing a light dose of 10 J/cm2 to samples containing 5μM indocyanine green, it is possible to inactivate S. pneumoniae and efficiently assist the phagocytic action of macrophages.
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Agarwal, Vaibhav. "Role of PspC interaction with human polymeric immunoglobulin receptor and Factor H in Streptococcus pneumoniae infections and host cell induced signalling." kostenfrei, 2008. http://www.opus-bayern.de/uni-wuerzburg/volltexte/2009/3652/.
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Lores, Lazara Elena Santiesteban. "Síntese, caracterização e avaliação imunológica de conjugados do sorotipo 6B de Streptococcus pneumoniae à proteína A de superfície pneumocócica (PspA)." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-19062017-151232/.
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As vacinas conjugadas contra Streptococcus pneumoniae mostram-se eficazes na redução da doença pneumocócica, no entanto depois de sua introdução tem se verificado a substituição de sorotipos. Para evitar estes problemas o emprego de proteínas da própria bactéria como carreadoras tem sido usado. Neste trabalho a PspA foi conjugada ao sorotipo 6B de S. pneumoniae por dois métodos de conjugação. Inicialmente a PspA clado 1 e 3 foram purificadas, recuperando as proteínas com mais de 90% de pureza. A conjugação intermediada pelo agente ativador cloreto de 4-(4,6-dimetoxi-1,3,5-triazin-2-il-)-4-metilmorfolino (DMT-MM) permitiu rendimentos de Ps entre 20 e 30%, no entanto este tipo de conjugado não foi imunogênico resultando na não indução de anticorpos anti-PspA. Por outro lado a conjugação por aminação redutiva possibilitou obter rendimentos de Ps entre 50 e 60% e os conjugados induziram elevados títulos de anticorpos anti-PspA em camundongos Balb/c, que foram capazes de promover a fagocitose da bactéria; no entanto, a resposta de anticorpos anti-Ps 6B foi baixa.<br>Conjugate vaccines against Streptococcus pneumonaie have had an important public health benefit; nevertheless after its introduction it has been observed a serotype replacement. To solve this problems conjugate vaccines using pneumococcal surface proteins as carriers has been studied. In this work, Pneumococal surface protein A (PspA) was employed as a carrier protein, conjugated to serotype 6B. Initially PspA clade 1 and PspA clade 3 were purified; both proteins were recovered with more than 90% purity. The conjugation mediated by the activating agent 4- (4,6-dimethoxy-1,3,5-triazin-2-yl -) - 4-methylmorpholine chloride(DMT-MM) allowed Ps yields between 20 and 30%, however this conjugation chemistry had a negative impact on the immunogenicity of the protein. On the other hand conjugation by reductive amination led to Ps yields between 50 and 60% and induced high anti-PspA antibodies titers in Balb /c mice that were able to promote phagocytosis of the bacterium; however, polysaccharide 6B induced low antibody titers.
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Piroth, Lionel. "Apports d'un modèle de pneumonie expérimentale bactériémique à streptococcus pneumoniae de sensibilité diminuée à la pénicilline dans la prise en charge des pneumonies humaines." Dijon, 2001. http://www.theses.fr/2001DIJOMU02.
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Strpetococcus pneumoniae est l'un des pathogenes les plus frequemment responsables de pneumonies bacteriemiques, avec une morbidite et une mortalite consequentes. L'incidence des souches de s. Pneumoniae de sensibilite diminuee a la penicilline et a d'autres antibiotiques est en constante augmentation. Ces donnees et les problemes therapeutiques inherents soulignent l'importance d'une meilleure connaissance des relations hote-pathogene-antibiotique, que seuls les modeles experimentaux permettent d'approfondir significativement. Nous avons pu developper un modele reproductible et simple de pneumonie chez le lapin immuno-competent, par instillation endo-bronchique d'un inoculum de s. Pneumoniae resistant a la penicilline, sans utilisation d'adjuvants pro-inflammatoires. La pneumonie bacteriemique ainsi obtenue reproduit fidelement les caracteristiques observees chez l'homme, tant sur les plans clinique, radiologique, histologique que microbiologique. Nous avons pu egalement reproduire la cinetique humaine plasmatique des antibiotiques par administration continue controlee par ordinateur. Ce modele, qui permet donc d'obtenir avec des souches d'origine humaine une pneumonie bacteriemique proche de celle observee chez l'homme et de realiser un traitement antibiotique humanise, a ete utilise sur plus de 200 animaux.
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Bennett, Allison E. "Characterization of sortase and its effect on the virulence of Streptococcus pneumoniae." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008d/bennet.pdf.
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Bui, Nhat Khai. "Characterisation of cell wall enzymes from Streptococcus pneumoniae." Thesis, University of Newcastle Upon Tyne, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556139.
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Murein and its turnover products are recognised by components of the innate immune system leading to an inflammatory response and resulting in the killing of bacteria. To counter the clearance by the innate immune system pathogens like Streptococcus pneumoniae have enzymes to modify their cell wall so that they are no longer recognised. The most common modifications are the N-deacetylation and O-acetylation of the glycan strands in the murein. Deacetylated murein was shown to be a poor substrate for lysozyme which is an important factor of the innate immune system capable of lysing sensitive bacteria that have unmodified murein. The single pneumococcal protein responsible for the deacetylation of murein is the murein N- acetylglucosamine deacetylase A (PgdA). Thus PgdA is a possible target for antibacterial therapy. An economical and ease-to-use assay is required to screen for inhibitors of PgdA. Within this work, such an assay has been established using recombinant PgdA with chromogenic substrates. For the first time the activity of purified PgdA with a natural substrate, murein from S. pneumoniae, has been demonstrated. Another interesting candidate as a possible target for inhibitors is the putative murein hydrolase PcsB. However, there are no biochemical data available yet, and in silico comparison and deletion mutants gave only vague hints for a hypothetical function as murein hydrolase. In this work a recombinant, soluble version of PcsB was purified. It showed no significant enzymatic activity against pneumococcal cell wall or murein.
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Hemsley, Carolyn. "Investigation of virulence gene regulation in Streptococcus pneumoniae." Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410462.
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Streptococcus pneumoniae is an important human pathogen in all age groups worldwide that causes a variety of diseases, ranging from life threatening septicaemia and meningitis to less severe sinusitis and otitis media. The factors that determine the virulence of S. pneumoniae are very complex but a key aspect of the organism's disease causing potential is the ability of the bacteria to regulate virulence factor expression and activity. In this study two main approaches were taken to investigate virulence gene expression in S. pneumoniae. Firstly, the feasibility of Recombinase based In vivo Expression Technology, RIVET, for use in S. pneumoniae to study gene expression in vitro, and then in vivo was assessed. However, the system was found to be unsuitable for use in this study. Secondly, the requirement for and the role of virulence gene regulators identified by Signature Tagged Mutagenesis were investigated. The requirement for different virulence gene regulators varied according to the murine model of infection used. Two of the regulators, MgrA and R1rA, were essential for nasopharyngeal carriage and production of pneumonia in mice by serotype 4 S. Pneumoniae. Both were shown to control the transcription of genes of a newly described pathogenicity islet, PPI2, encoding R1rA and proteins predicted to act at the bacterial cell surface. The PPI2 genes rlrA and rrgA were shown to be required for adhesion of serotype 4 S. pneumoniae to human epithelial cells and PPI2 gene expression was affected by the gaseous composition of the growth environment in an MgrA dependent manner. The distribution of MgrA, R1rA and PPI2 varied between clinical S. pneumoniae isolates emphasizing the likelihood of a different repertoire of virulence genes and regulators amongst different serotypes and strains of this important human pathogen.
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Reid, Nicholas. "Clinical, microbiological and molecular epidemiology of Streptococcus pneumoniae." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311200.
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<I>Streptococcus pneumoniae</I> is a serious pathogen, responsible for a large proportion of cases of pneumonia, bacteraemia and meningitis. Restriction endonuclease analysis (REA) using <I>Taq </I>I and <I>Hae</I> III was evaluated to analyse the genetic relationships among 51 isolates of <I>S. pneumoniae</I> in four different serotypes. This method was used together with pulsed-field gel electrophoresis (PFGE) in the analysis of clinical isolates of bacteraemic <I>S. pneumoniae</I> in the Grampian region of Scotland during a two year period from 1993-5. A total of 104 isolates were collected, of which 93 were analysed by REA and 94 by PFGE. Sensitivities to eight commonly used antibiotics were determined for 99 isolates, and serotyping was performed by the relevant reference laboratory. Records were available for 92 patients and details of past medical history, primary site of infection and outcome were abstracted. Of the clinical isolates analysed, 1% were fully resistant to penicillin and 12% were resistant to erythromycin. The three most common serotypes were 14(23.5%), 4 (12.2%) and 23F (9.2%). The current vaccine, Pneumovax II, was calculated to provide 99.8% cover for the serotypes isolated. The overall incidence of bacteraemic infection was 10.3 per 100,000 population per year, and the mortality was 21.2%. Both the incidence and mortality increased exponentially with respect to age. In both serotype and clinically based studies, when analysed by REA and PFGE, isolates were primarily grouped into closely associated clusters of single serotypes. Some serotypes, such as 3, 6B and 14, were divided into genetically distinct subgroups. The genetics structure of the population was defined as being primarily clonal with evidence of a serotype change in one instance. An erythromycin resistant serotype 14 clone was described, and later discovered to be of the M phenotype. This clone was significantly associated with bacteraemic disease in the under 5 age group, and was demonstrated to be the current major cause of erythromycin resistance in the U.K.
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Campbell, James. "Utilisation of glycoprotein-derived carbohydrates by streptococcus pneumoniae." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410339.
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