Academic literature on the topic 'Β-lactamases'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Β-lactamases.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Β-lactamases"
1
Sauvage, Eric, Eveline Fonzé, Birgit Quinting, Moreno Galleni, Jean-Marie Frère, and Paulette Charlier. "Crystal Structure of the Mycobacterium fortuitum Class A β-Lactamase: Structural Basis for Broad Substrate Specificity." Antimicrobial Agents and Chemotherapy 50, no. 7 (July 2006): 2516–21. http://dx.doi.org/10.1128/aac.01226-05.
Full textAbstract:
ABSTRACT β-Lactamases are the main cause of bacterial resistance to penicillins and cephalosporins. Class A β-lactamases, the largest group of β-lactamases, have been found in many bacterial strains, including mycobacteria, for which no β-lactamase structure has been previously reported. The crystal structure of the class A β-lactamase from Mycobacterium fortuitum (MFO) has been solved at 2.13-Å resolution. The enzyme is a chromosomally encoded broad-spectrum β-lactamase with low specific activity on cefotaxime. Specific features of the active site of the class A β-lactamase from M. fortuitum are consistent with its specificity profile. Arg278 and Ser237 favor cephalosporinase activity and could explain its broad substrate activity. The MFO active site presents similarities with the CTX-M type extended-spectrum β-lactamases but lacks a specific feature of these enzymes, the VNYN motif (residues 103 to 106), which confers on CTX-M-type extended-spectrum β-lactamases a more efficient cefotaximase activity.
2
Williams, J. D. "β-Lactamases and β-lactamase inhibitors." International Journal of Antimicrobial Agents 12 (August 1999): S3—S7. http://dx.doi.org/10.1016/s0924-8579(99)00085-0.
Full text
3
Pradel, N., J. Delmas, L. F. Wu, C. L. Santini, and R. Bonnet. "Sec- and Tat-Dependent Translocation of β-Lactamases across the Escherichia coli Inner Membrane." Antimicrobial Agents and Chemotherapy 53, no. 1 (November 3, 2008): 242–48. http://dx.doi.org/10.1128/aac.00642-08.
Full textAbstract:
ABSTRACT β-Lactamases represent the major resistance mechanism of gram-negative bacteria against β-lactam antibiotics. The amino acid sequences of these proteins vary widely, but all are located in the periplasm of bacteria. In this study, we investigated the translocation mechanism of representative β-lactamases in an Escherichia coli model. N-terminal signal sequence analyses, antibiotic activity assay, and direct measurement of translocation of a green fluorescent protein (GFP) reporter fused to β-lactamases revealed that most were exported via the Sec pathway. However, the Stenotrophomonas maltophilia L2 β-lactamase was exported via the E. coli Tat translocase, while the S. maltophilia L1 β-lactamase was Sec dependent. These results show the possible Tat-dependent translocation of β-lactamases in the E. coli model system. In addition, the mutation of the cytoskeleton-encoding gene mreB, which may be involved in the spatial organization of penicillin-binding proteins, decreased the MIC of β-lactams for β-lactamase-producing E. coli. These findings provide new knowledge about β-lactamase translocation, a putative new target for addressing β-lactamase-mediated resistance.
4
Thomson, Kenneth S., Christine C. Sanders, and Ellen Smith Moland. "Use of Microdilution Panels with and without β-Lactamase Inhibitors as a Phenotypic Test for β-Lactamase Production among Escherichia coli, Klebsiella spp.,Enterobacter spp., Citrobacter freundii, andSerratia marcescens." Antimicrobial Agents and Chemotherapy 43, no. 6 (June 1, 1999): 1393–400. http://dx.doi.org/10.1128/aac.43.6.1393.
Full textAbstract:
ABSTRACT Over the past decade, a number of new β-lactamases have appeared in clinical isolates of Enterobacteriaceaethat, unlike their predecessors, do not confer β-lactam resistance that is readily detected in routine antibiotic susceptibility tests. Because optimal methodologies are needed to detect these important new β-lactamases, a study was designed to evaluate the ability of a panel of various β-lactam antibiotics tested alone and in combination with β-lactamase inhibitors to discriminate between the production of extended-spectrum β-lactamases, AmpC β-lactamases, high levels of K1 β-lactamase, and other β-lactamases in 141 isolates of Escherichia coli,Klebsiella pneumoniae, Klebsiella oxytoca,Enterobacter cloacae, Enterobacter aerogenes,Citrobacter freundii, and Serratia marcescens possessing well-characterized β-lactamases. The microdilution panels studied contained aztreonam, cefpodoxime, ceftazidime, cefotaxime, and ceftriaxone, with and without 1, 2, and 4 μg of clavulanate per ml or 8 μg of sulbactam per ml and cefoxitin and cefotetan with and without 8 μg of sulbactam per ml. The results indicated that a minimum panel of five tests would provide maximum separation of extended-spectrum β-lactamase high AmpC, high K1, and other β-lactamase production in Enterobacteriaceae. These included cefpodoxime, cefpodoxime plus 4 μg of clavulanate per ml, ceftazidime, ceftriaxone, and ceftriaxone plus 8 μg of sulbactam per ml. Ceftriaxone plus 2 μg of clavulanate per ml could be substituted for cefpodoxime plus 4 μg of clavulanate per ml without altering the accuracy of the tests. This study indicated that tests with key β-lactam drugs, alone and in combination with β-lactamase inhibitors, could provide a convenient approach to the detection of a variety of β-lactamases in members of the family Enterobacteriaceae.
5
Rudgers, Gary W., Wanzhi Huang, and Timothy Palzkill. "Binding Properties of a Peptide Derived from β-Lactamase Inhibitory Protein." Antimicrobial Agents and Chemotherapy 45, no. 12 (December 1, 2001): 3279–86. http://dx.doi.org/10.1128/aac.45.12.3279-3286.2001.
Full textAbstract:
ABSTRACT To overcome the antibiotic resistance mechanism mediated by β-lactamases, small-molecule β-lactamase inhibitors, such as clavulanic acid, have been used. This approach, however, has applied selective pressure for mutations that result in β-lactamases no longer sensitive to β-lactamase inhibitors. On the basis of the structure of β-lactamase inhibitor protein (BLIP), novel peptide inhibitors of β-lactamase have been constructed. BLIP is a 165-amino-acid protein that is a potent inhibitor of TEM-1 β-lactamase (K i = 0.3 nM). The cocrystal structure of TEM-1 β-lactamase and BLIP indicates that residues 46 to 51 of BLIP make critical interactions with the active site of TEM-1 β-lactamase. A peptide containing this six-residue region of BLIP was found to retain sufficient binding energy to interact with TEM-1 β-lactamase. Inhibition assays with the BLIP peptide reveal that, in addition to inhibiting TEM-1 β-lactamase, the peptide also inhibits a class A β-lactamase and a class C β-lactamase that are not inhibited by BLIP. The crystal structures of class A and C β-lactamases and two penicillin-binding proteins (PBPs) reveal that the enzymes have similar three-dimensional structures in the vicinity of the active site. This similarity suggests that the BLIP peptide inhibitor may have a broad range of activity that can be used to develop novel small-molecule inhibitors of various classes of β-lactamases and PBPs.
6
Liang, Yu-He, Rong Gao, and Xiao-Dong Su. "Structural insights into the broadened substrate profile of the extended-spectrum β-lactamase OXY-1-1 fromKlebsiella oxytoca." Acta Crystallographica Section D Biological Crystallography 68, no. 11 (October 18, 2012): 1460–67. http://dx.doi.org/10.1107/s090744491203466x.
Full textAbstract:
Klebsiella oxytocais a pathogen that causes serious infections in hospital patients. It shows resistance to many clinically used β-lactam antibiotics by producing chromosomally encoded OXY-family β-lactamases. Here, the crystal structure of an OXY-family β-lactamase, OXY-1-1, determined at 1.93 Å resolution is reported. The structure shows that the OXY-1-1 β-lactamase has a typical class A β-lactamase fold and exhibits greater similarity to CTX-M-type β-lactamases than to TEM-family or SHV-family β-lactamases. It is also shown that the enzyme provides more space around the active cavity for theR1andR2substituents of β-lactam antibiotics. The half-positive/half-negative distribution of surface electrostatic potential in the substrate-binding pocket indicates the preferred properties of substrates or inhibitors of the enzyme. The results reported here provide a structural basis for the broadened substrate profile of the OXY-family β-lactamases.
7
Gupta, Tanushree Barua, Malini Shariff, Thukral Ss, and S. s. Thukral. "IDENTIFICATION OF AMPC Β-LACTAMASE-PRODUCING CLINICAL ISOLATES OF ESCHERICHIA COLI." Asian Journal of Pharmaceutical and Clinical Research 10, no. 12 (December 1, 2017): 357. http://dx.doi.org/10.22159/ajpcr.2017.v10i12.21648.
Full textAbstract:
Objective: Indiscriminate use of β-lactam antibiotics has resulted in the emergence of β-lactamase enzymes. AmpC β-lactamases, in particular, confer resistance to penicillin, first-, second-, and third-generation cephalosporins as well as monobactams and are responsible for antibiotic resistance in nosocomial pathogens. Therefore, this study was undertaken to screen nosocomial Escherichia coli isolates for the presence and characterization of AmpC β-lactamases. The study also envisaged on the detection of inducible AmpC β-lactamases and extended-spectrum β-lactamases (ESBLs) in AmpC β-lactamase-producing E. coli.Methods: A total of 102 clinical isolates of E. coli, were subjected to cefoxitin screening, and screen-positive isolates were further subjected to inhibitor-based detection method, phenotypic confirmatory test, disc antagonism test, polymerase chain reaction (PCR), and isoelectric focusing (IEF).Results: In this study, 33% of E. coli were resistant to cefoxitin, of which 35% were found to be positive for AmpC β-lactamase by inhibitor-based phenotypic test. Of the AmpC-positive isolates, 83% were positive for ESBLs, whereas 25% were producing inducible AmpC β-lactamases. PCR and IEF showed CIT and EBC types of AmpC β-lactamases present in the tested isolates.Conclusion: Our study showed the presence of inducible AmpC enzymes and ESBLs in E. coli isolates and PCR identified more isolates to be AmpC producers.
8
MATAGNE, André, Josette LAMOTTE-BRASSEUR, and Jean-Marie FRÈRE. "Catalytic properties of class A β-lactamases: efficiency and diversity." Biochemical Journal 330, no. 2 (March 1, 1998): 581–98. http://dx.doi.org/10.1042/bj3300581.
Full textAbstract:
β-Lactamases are the main cause of bacterial resistance to penicillins, cephalosporins and related β-lactam compounds. These enzymes inactivate the antibiotics by hydrolysing the amide bond of the β-lactam ring. Class A β-lactamases are the most widespread enzymes and are responsible for numerous failures in the treatment of infectious diseases. The introduction of new β-lactam compounds, which are meant to be ‘β-lactamase-stable’ or β-lactamase inhibitors, is thus continuously challenged either by point mutations in the ubiquitous TEM and SHV plasmid-borne β-lactamase genes or by the acquisition of new genes coding for β-lactamases with different catalytic properties. On the basis of the X-ray crystallography structures of several class A β-lactamases, including that of the clinically relevant TEM-1 enzyme, it has become possible to analyse how particular structural changes in the enzyme structures might modify their catalytic properties. However, despite the many available kinetic, structural and mutagenesis data, the factors explaining the diversity of the specificity profiles of class A β-lactamases and their amazing catalytic efficiency have not been thoroughly elucidated. The detailed understanding of these phenomena constitutes the cornerstone for the design of future generations of antibiotics.
9
Drawz, Sarah M., and Robert A. Bonomo. "Three Decades of β-Lactamase Inhibitors." Clinical Microbiology Reviews 23, no. 1 (January 2010): 160–201. http://dx.doi.org/10.1128/cmr.00037-09.
Full textAbstract:
SUMMARYSince the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial β-lactamases. β-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome β-lactamase-mediated resistance, β-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner β-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of seriousEnterobacteriaceaeand penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to β-lactam-β-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant β-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of β-lactams. Here, we review the catalytic mechanisms of each β-lactamase class. We then discuss approaches for circumventing β-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of β-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a “second generation” of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of β-lactamases.
10
Lahiri, Sushmita D., and Richard A. Alm. "Identification of Novel VEB β-Lactamase Enzymes and Their Impact on Avibactam Inhibition." Antimicrobial Agents and Chemotherapy 60, no. 5 (February 29, 2016): 3183–86. http://dx.doi.org/10.1128/aac.00047-16.
Full textAbstract:
ABSTRACTCeftazidime-avibactam has activity againstPseudomonas aeruginosaandEnterobacteriaceaeexpressing numerous class A and class C β-lactamases, although the ability to inhibit many minor enzyme variants has not been established. Novel VEB class A β-lactamases were identified during characterization of surveillance isolates. The cloned novel VEB β-lactamases possessed an extended-spectrum β-lactamase phenotype and were inhibited by avibactam in a concentration-dependent manner. The residues that comprised the avibactam binding pocket were either identical or functionally conserved. These data demonstrate that avibactam can inhibit VEB β-lactamases.
Dissertations / Theses on the topic "Β-lactamases"
1
Zavala, Agustin. "Structure-function studies of β-lactamases." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS567.
Full textAbstract:
La résistance antimicrobienne est devenue un problème majeur de santé publique. L’usage parfois abusif d’antibiotiques conduit à la sélection et à la propagation mondiale de mécanismes de résistance. Grâce à leur efficacité clinique et faible toxicité, les β-lactamines sont les antibiotiques les plus prescrits actuellement, et le mécanisme de résistance le plus répandu est l’expression de β-lactamases. Dans ces conditions, le développement de nouveaux traitements antimicrobiens, pour des cibles connues ou nouvelles, est essentiel. Plus particulièrement, le développement de nouveaux inhibiteurs des β-lactamases est très prometteur, permettant de continuer l’utilisation des antibiotiques existants. Les études biochimiques et structurales des nouvelles β-lactamases et leurs mutants synthétiques, par cristallographie aux rayons X ou par différentes techniques de modélisation moléculaire (modélisation par homologie, « docking », dynamique moléculaire, analyse du réseau des molécules d’eau) permettent une meilleure compréhension de ces enzymes. Dans ce contexte, nous avons caractérisé plusieurs β-lactamases du point de vue phénotypique, biochimique et structural.La β-lactamase CMY-136 contient une mutation inhabituelle, Y221H, par rapport à CMY-2, dans une position qui est très conservée parmi les enzymes de classe C. Les études cristallographiques et de modélisation moléculaire ont révélé des interactions stériques défavorables autour de la position mutée 221 qui peuvent affecter la conformation et la dynamique de la boucle Ω, et qui pourraient expliquer l’hydrolyse plus efficace des substrats volumineux et l’affinité plus faible de la plupart des substrats par rapport à la CMY-2.La structure cristallographique de la β-lactamase OXA-427, une nouvelle carbapénèmase de classe D, montre une Lys73 très peu carbamoylée, ce qui est très inhabituel pour cette classe d’enzyme, ainsi qu’un pont hydrophobe à proximité du site actif. Les simulations de dynamique moléculaire ont montré que la boucle β5-β6 est plus flexible et dans une conformation étendue. Ces résultats peuvent expliquer le profil d’hydrolyse unique observé expérimentalement pour cette enzyme.Les modifications dans la boucle β5-β6 de la β-lactamase OXA-48 (mutations d’alanines, délétions systematiques, remplacement par la boucle β5-β6 de la β-lactamase OXA-18) provoquent des modifications importantes dans le profil d’hydrolyse, avec une acquisition graduelle d’une activité cephalosporinase et une diminution de l’activité carbapénémase dans certains cas. Des études de cristallographie aux rayons X et modélisation moléculaire suggèrent que les différences de conformation et de flexibilité dans cette boucle et les régions adjacentes permettent une meilleure fixation des céphalosporines plus volumineuses, par rapport à l’OXA-48. L’analyse de la dynamique des molécules d’eau dans le site actif montre des changements qui sont potentiellement responsables de la diminution de l’activité par rapport aux carbapénèmes. En complément des études sur les mutants naturels, ces résultats confirment l’importance de la boucle β5-β6 pour la spécificité de substrat des enzymes de type OXA-48. La structure cristallographique du mutant 217ΔP de l’OXA-48 présente une conformation auto-inhibée inattendue, induite par la présence d’un ion nitrate, un inhibiteur auparavant inconnu des β-lactamases de classe D.La Beta-Lactamase DataBase(BLDB, http://bldb.eu) développée dans notre équipe est une ressource publique exhaustive contenant des données relatives aux β-lactamases, vérifiées et mises à jour régulièrement. Cette base de données contient tous les mutants naturels et synthétiques de β-lactamases, ainsi que toutes les structures 3D disponibles dans la PDB et la caractérisation phénotypique.Globalement, ces résultats représentent le prérequis pour une meilleure compréhension des relations structure-fonction des β-lactamases et pour le futur développement rationnel d’inhibiteurs pour ces enzymesAntimicrobial resistance (AMR) has become a major threat to public health nowadays. The use and abuse of antibiotics is increasingly leading to selection and spread of resistance mechanisms worldwide, greatly compromising our capacity to treat infectious diseases. AMR might ultimately result in a future without effective antimicrobial therapy. Due to their safety and clinical efficacy, β-lactams are the most utilized antimicrobial therapy, and the most common resistance mechanism is the expression of β-lactamases. Therefore, the development of new antimicrobial drugs, for novel or already known targets, is of utmost importance. In particular, the development of novel inhibitors towards β-lactamases is also quite promising, as it would allow us to continue using the effective and safe antimicrobial drugs already available today. The biochemical and structural study of novel β-lactamases or synthetic mutants, through X-ray crystallography and various molecular modelling techniques (homology modelling, docking, molecular dynamics, water network analysis), can provide valuable information. In this context, we have characterized phenotypically, biochemically and structurally several β-lactamases.The CMY-136 β-lactamase possesses an unusual mutation, Y221H, as compared to CMY-2, in a position highly conserved among class C ß-lactamases. Crystallographic and molecular modelling experiments reveal a steric impediment around the mutated position 221 that may affect the conformation and dynamics of the Ω-loop, and therefore account for an increased turnover rate for bulky substrates and a decreased affinity for most substrates as compared to CMY-2.The crystal structure of the OXA-427, a novel class D carbapenemase, shows the Lys73 only partially carbamoylated, a very unusual characteristic for this class of β-lactamases, and an unexpected hydrophobic bridge in the vicinity of the active site. Moreover, molecular dynamics simulations revealed an extended and highly flexible β5-β6 loop. Altogether, these features may explain the unique hydrolytic profile determined experimentally for this enzyme.Modifications in the β5-β6 loop of the OXA-48 β-lactamase (alanine scanning, systematic deletions, replacement with the β5-β6 loop from OXA-18) result in profound changes in the hydrolytic profile, with gradual acquisition of cephalosporinase activity and decrease of carbapenemase activity in some cases. X-ray crystallography and molecular modelling studies suggest that the altered conformation and flexibility of this loop and of adjacent regions in these mutants may allow for the better accommodation of the bulkier cephalosporins, compared to OXA-48. Additionally, water dynamics analysis highlighted changes in the water network around and inside the active site cavity that may be responsible for the lower activity towards carbapenems. Together with studies on other naturally occurring mutants, results corroborate the relevance of the β5-β6 loop on the substrate profile of OXA-type enzymes. Crystal structure of the OXA-48 217ΔP mutant reveals an unexpected self-inhibited conformation induced by the presence of a nitrate ion, a previously unknown inhibitor of class D β-lactamases.Finally, the Beta-Lactamase DataBase (BLDB, http://bldb.eu) developed in our laboratory is a comprehensive, manually curated public resource providing up-to-date structural and functional information on β-lactamases. It contains all reported naturally-occurring β-lactamases and synthetic mutants, together with all available 3D structures from the PDB and the phenotypical characterization.Overall, these results constitute an essential foundation for a better understanding of the structure-function relationship of β-lactamases, which may prove crucial for the future rational development of β-lactamase inhibitors
2
Hammond, David Scott. "SHV β-lactamases : DNA diagnostics and evolution." Thesis, Queensland University of Technology, 2006. https://eprints.qut.edu.au/16194/1/David_Hammond_Thesis.pdf.
Full textAbstract:
TEM and SHV β-lactamases are the most prevalent β-lactamases among Gram-negative bacteria. The introduction and widespread use of expanded-spectrum antibiotics, particularly third generation cephalosporins, has led to the evolution of bacterial strains expressing extended spectrum β-lactamases (ESBLs). ESBLs emerge by genetic point mutation from non-extended spectrum precursors.
It was found that multiple β-lactamase families within single isolates complicate the process of detecting the resistance status of isolate using non-quantitative DNA diagnostic methods. Preliminary phenotypic characterisation of probable β-lactamase enzyme family types present in 100 isolates from the Asia-Pacific and South African locales showed that single isolates frequently contained multiple β-lactamase families. SHV, TEM, AMPC and CTX-M β-lactamase families were detected in these isolates using PCR detection methods. Ninety-eight percent of all isolates tested contained as least one β-lactamase gene, with up to four to β-lactamase gene families found to co-exist in single isolates. Kinetic PCR methods for interrogating the polymorphic sites at blaSHV codons 238 & 240 and blaTEM codons 164, 238, 240 as well as promoter polymorphism were developed. A high proportion of blaSHV 238 and 240 mutant alleles was found to correlate with cefotaxime, ceftazidime and aztreonam resistance levels.
In an attempt to understand the molecular basis for the co-existence of multiple blaSHV alleles within single isolates, the blaSHV promoter region was cloned from one ESBL expressing isolate. Experimental results showed that blaSHV can exist downstream of two different promoters within a single isolate. Both promoters have previously been reported, and differ by the presence or absence of IS26, which results in a change in the transcription initiation site. The blaSHV gene copy numbers in cis with the different promoters were measured, and it was found that the copy number of the IS26::blaSHV promoter was positively correlated with resistance levels.
Cloning and analysis of PCR products showed that different blaSHV variants existed in cis with promoters in individual isolates. However, mutant genes were more abundant downstream of the IS26 promoter. There were no ESBL+ isolates without this promoter. It was concluded that blaSHV in cis with the IS26 promoter is located on an amplifiable replicon, and the presence of the IS26 insertion may facilitate the acquisition of an ESBL+ phenotype.
To further confirm the role of IS26 in resistance acquisition, ESBL negative isolates were subjected to serial passage in vitro evolution experiments and fluctuation assays. Results confirm that the insertion of the IS26 element upstream of blaSHV is positively correlated with the ability to exhibit an ESBL phenotype, when such isolates also contain the critical G238S substitution. It was also found that IS26 can catalyse the duplication and mobilisation of blaSHV within an isolate. Fluctuation experiments have shown that the frequency at which such genomic events occur resulting in ESBL phenotypes is extremely low and requires many generations of selection under sub-lethal conditions.
A survey of a geographically diverse set of isolates has shown that IS26-blaSHV was found in all of the bacterial populations surveyed. However, it does not appear to be exclusively associated with SHV-mediated ESBL production.
3
Hammond, David Scott. "SHV β-lactamases : DNA diagnostics and evolution." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16194/.
Full textAbstract:
TEM and SHV β-lactamases are the most prevalent β-lactamases among Gram-negative bacteria. The introduction and widespread use of expanded-spectrum antibiotics, particularly third generation cephalosporins, has led to the evolution of bacterial strains expressing extended spectrum β-lactamases (ESBLs). ESBLs emerge by genetic point mutation from non-extended spectrum precursors. It was found that multiple β-lactamase families within single isolates complicate the process of detecting the resistance status of isolate using non-quantitative DNA diagnostic methods. Preliminary phenotypic characterisation of probable β-lactamase enzyme family types present in 100 isolates from the Asia-Pacific and South African locales showed that single isolates frequently contained multiple β-lactamase families. SHV, TEM, AMPC and CTX-M β-lactamase families were detected in these isolates using PCR detection methods. Ninety-eight percent of all isolates tested contained as least one β-lactamase gene, with up to four to β-lactamase gene families found to co-exist in single isolates. Kinetic PCR methods for interrogating the polymorphic sites at blaSHV codons 238 & 240 and blaTEM codons 164, 238, 240 as well as promoter polymorphism were developed. A high proportion of blaSHV 238 and 240 mutant alleles was found to correlate with cefotaxime, ceftazidime and aztreonam resistance levels. In an attempt to understand the molecular basis for the co-existence of multiple blaSHV alleles within single isolates, the blaSHV promoter region was cloned from one ESBL expressing isolate. Experimental results showed that blaSHV can exist downstream of two different promoters within a single isolate. Both promoters have previously been reported, and differ by the presence or absence of IS26, which results in a change in the transcription initiation site. The blaSHV gene copy numbers in cis with the different promoters were measured, and it was found that the copy number of the IS26::blaSHV promoter was positively correlated with resistance levels. Cloning and analysis of PCR products showed that different blaSHV variants existed in cis with promoters in individual isolates. However, mutant genes were more abundant downstream of the IS26 promoter. There were no ESBL+ isolates without this promoter. It was concluded that blaSHV in cis with the IS26 promoter is located on an amplifiable replicon, and the presence of the IS26 insertion may facilitate the acquisition of an ESBL+ phenotype. To further confirm the role of IS26 in resistance acquisition, ESBL negative isolates were subjected to serial passage in vitro evolution experiments and fluctuation assays. Results confirm that the insertion of the IS26 element upstream of blaSHV is positively correlated with the ability to exhibit an ESBL phenotype, when such isolates also contain the critical G238S substitution. It was also found that IS26 can catalyse the duplication and mobilisation of blaSHV within an isolate. Fluctuation experiments have shown that the frequency at which such genomic events occur resulting in ESBL phenotypes is extremely low and requires many generations of selection under sub-lethal conditions. A survey of a geographically diverse set of isolates has shown that IS26-blaSHV was found in all of the bacterial populations surveyed. However, it does not appear to be exclusively associated with SHV-mediated ESBL production.
4
Robin, Frédéric Gérard Jean Michel. "Exploration moléculaire, biochimique et structurale de β-lactamases à spectre étendu de sensibilité diminuée aux inhibiteurs des β-lactamases." Clermont-Ferrand 1, 2007. http://www.theses.fr/2007CLF1MM16.
Full textAbstract:
L'utilisation intensive de nouvelles β-lactamines comme les céphalosporines de 3ème génération (C3G) ou les inhibiteurs des β-lactamases a entraîné l'évolution des β-lactamases. Ainsi au cours des années 80-90 ont émergé les β-lactamases de spectre étendu (BLSE), capables d'hydrolyser les C3G, et les pénicillinases résistantes aux inhibiteurs (PRI). Enfin, depuis la fin des années 90, 4 enzymes associant des substitutions observées chez les BLSE et chez les PRI ont été décrites. Ainsi, des souches produisant de telles enzymes pourraient devenir plus difficilement détectables par les tests utilisés en routine et donc conduire à des échecs thérapeutiques. Notre travail s'inscrit dans l'étude de ces nouvelles enzymes, encore rarement rapportées. Cette étude nous a permis de décrire 4 nouveaux Mutants Complexes dérivés de la β-lactamase TEM-1 (TEM-109, TEM-125, TEM-151 et TEM-152) à partir de souches d'E. Coli isolées entre 2001 et 2004. Parmi ces enzymes, toutes présentaient une activité sur les C3G, mais seuls TEM-125 et TEM-152 avaient un niveau de résistance aux inhibiteurs élevé proche de celui d'enzymes de type PRI. Enfin, l'étude structurale et fonctionnelle de la BLSE résistante au tazobactam BES-1 a permis de mettre en évidence un certain nombre d'originalités structurales expliquant son activité atypique, comme un élargissement des parois du site actif et des interactions réalisées par le résidu Arg220, notamment avec la Thr237. Notre étude suggère donc l'émergence de ces nouvelles enzymes et fournit des données structurales nécessaires à la mise au point de nouvelles molécules antibiotiques ou inhibitrices.
5
Guillon, Hélène. "Activité carbapénémase des β-lactamases de type AmpC." Amiens, 2013. http://www.theses.fr/2013AMIED003.
Full textAbstract:
Les β-lactamases de type AmpC (céphalosporinases) semblent fréquemment responsables de la résistance aux carbapénèmes chez les entérobactéries, ce que permettent d’évoquer de nombreuses descriptions cliniques. L’objectif de cette thèse était d’effectuer une caractérisation phénotypique, biochimique et moléculaire de l’activité carbapénémase des AmpC. Tout d’abord, les gènes des cinq principales céphalosporinases plasmidiques ont été clonés puis transformés dans la souche imperméable Escherichia coli HB4. Les comparaisons phénotypiques et structurales des clones recombinants ont montré que les céphalosporinases CMY-2, ACT-1, et DHA-1 se distinguent des autres enzymes par leur capacité à conférer une résistance aux carbapénèmes et par la présence d’une asparagine en position 346 (Asn 346), située à proximité du site catalytique. Des expériences de mutagénèse dirigée, consistant à substituer l'Asn 346 par des résidus de taille, de charge et de polarité différentes dans la céphalosporinase CMY-2, ont démontré le rôle de cet acide aminé dans l’activité carbapénémase des céphalosporinases. La caractérisation biochimique de trois variants a révélé que l'Asn 346 contribue à l’affinité de CMY-2 pour l'imipénème. L'étude de l’activité carbapénémase des AmpC chromosomiques à spectre étendu (ACSE) a constitué le second volet de la thèse. Le séquençage, le clonage et la caractérisation biochimique d'une nouvelle ACSE produite par une souche clinique de E. Coli résistante à l'ertapénème ont démontré que l'extension du spectre d'hydrolyse des céphalosporinases, qui est due à une augmentation de leur affinité, peut être aussi responsable d'une résistance aux carbapénèmesOwing to several clinical reports, it appears that AmpC-type β-lactamases (cephalosporinases) account frequently for carbapenem resistance in Enterobacteriaceae. The aim of this study was to perform a phenotypic, biochemical, and molecular characterization of the carbapenem-hydrolyzing activity of AmpC-type β-lactamases. First of all, the genes encoding the five main plasmid-mediated AmpC β-lactamases were cloned and transferred into the porin-deficient Escherichia coli HB4 strain. Phenotypic and molecular comparison of the recombinant strains revealed that only CMY-2, ACT-1, and DHA-1 conferred resistance to carbapenems and had an asparagine residue at position 346 (Asn 346), located in the vicinity of the active site. Site-directed mutagenesis experiments were performed to replace the Asn 346 residue of CMY-2 β-lactamase by amino acids differing in size, charge, and polarity. It confirmed the contribution of Asn 346 to the carbapenem-hydrolysing activity of cephalosporinases. Biochemical characterization of three variants revealed that Asn 346 assisted the binding of imipenem. The analysis of the carbapenem-hydrolyzing activity of chromosomal extended-spectrum AmpC β-lactamases (ESAC) constitutes the second part of this thesis. Sequencing, cloning and biochemical characterization of a novel ESAC produced by an ertapenem-resistant E. Coli clinical isolate demonstrated that the extension of the hydrolysis spectrum of cephalosporinases, which was due to increased affinity, may also contribute to carbapenem resistance
6
Bertoncheli, Claudia de Mello. "Identificação de metalo-β-lactamases em bacilos gram-negativos não fermentadores isolados no Hospital Universitário de Santa Maria." Universidade Federal de Santa Maria, 2008. http://repositorio.ufsm.br/handle/1/5877.
Full textAbstract:
Conselho Nacional de Desenvolvimento Científico e TecnológicoIn recent years, the isolation of bacteria producing β-lactamases has caused concern around the world, due to the fact these enzymes hydrolysis the ring β-lactam antimicrobials used in the main clinic. This aim of this study was asses the prevalence metallo-β-lactamases (MbL) in isolates of Pseudomonas aeruginosa and Acinetobacter baumannii obtained from patients admitted at the University Hospital of Santa Maria (HUSM). The profile of susceptibility for all isolates was evaluated by the disk diffusion method standardized by CLSI. The antimicrobial disks were distributed in a way that allows the identification of strains producers of AmpC and ESBL. For the identification of the producers of MbL the test of disk approximation with EDTA 0.1 M, EDTA 0,5M and acid 2-mercaptopropionic were performed. Isolates that did not have any of the mechanisms of resistance search were classified as multiresistant (MDR). The minimum inhibitory concentration (MIC) for ceftazidima, imipenem and polymyxin B was assessed by broth method microdilution for all isolated, according to CLSI. From January to June 2006, were obtained 32 isolates the P.aeruginosa and 41 the A. baumannii, the those 17 (23.29%) were β-lactamase AmpC-type producers, 11 (15.07%) were MbL producers, and 45 (61,64%) were classified as MDR. All strains producing MbL were Pseudomonas aeruginosa. The sensitivity of the isolates according to the CIM for antimicrobial evaluated were: 90,28% for polymyxin B, 36,11% for imipenem and 18% for ceftazidima. There was a high prevalence of MDR isolates and producers of β-lactamase-type AmpC and MbL in HUSM, this is extremely worrying once there is limiting therapy available. This situation becomes even more worrying with the find of isolates resistant the polymyxin B, witch is one of the last options of treatment for MDR isolates and producers of MbL. The detection of microorganisms is extremely important for the committees of infection hospital with the goal of preventing outbreaks, as well as guide the medical team on the conduct therapy, since there are few effective antimicrobial clinically for these pathogens and no prospects for development the new antimicrobial in the near future.
Nos últimos anos, o isolamento de bactérias produtoras de β-lactamases tem causado preocupação em todo o mundo, devido ao fato dessas enzimas hidrolisarem o anel β- lactâmico dos principais antimicrobianos utilizados na clínica. Este trabalho teve por objetivo avaliar a prevalência de metalo-β-lactamases (MbL) em isolados de Pseudomonas aeruginosa e Acinetobacter baumannii obtidos de pacientes atendidos no Hospital Universitário de Santa Maria (HUSM). O perfil de sensibilidade para todos os isolados foi avaliado pelo método de disco difusão padronizado pelo CLSI. Os discos de antimicrobianos utilizados foram distribuídos de forma que permitisse a identificação dos isolados produtores de AmpC e ESBL. Para a identificação dos produtores de MbL utilizou-se o teste de disco aproximação com os seguintes agentes quelantes: EDTA 0,1M, EDTA 0,5 M e ácido 2-mercaptopropiônico. Os isolados que não possuíam nenhum dos mecanismos de resistência pesquisados foram classificados como multirresistentes (MDR). A concentração inibitória mínima (CIM) para ceftazidima, imipenem e polimixina B foi avaliada pelo método de microdiluição em caldo para todos os isolados, de acordo com o CLSI. Durante o período de janeiro a junho de 2006 foram obtidos 32 isolados de P.aeruginosa e 41 de A. baumannii, destes 17 (23,29%) foram produtores de β-lactamase do tipo AmpC, 11 (15,07%) foram produtores de MbL e 45 (61,64%) foram classificados como MDR. Todas as cepas produtoras de MbL foram de Pseudomonas aeruginosa. A sensibilidade dos isolados de acordo com a CIM para os antimicrobianos avaliados foram as seguintes: 90,28% para polimixina B, 36,11% imipenem e 18% ceftazidima. Observou-se uma alta prevalência de isolados MDR no HUSM, além de isolados produtores de β-lactamase do tipo AmpC e MbL, o que é extremamente preocupante devido limitar a terapia a poucos antimicrobianos. Esta situação torna-se ainda mais preocupante com a detecção de isolados resistentes a polimixina B, a qual é uma das últimas opções de tratamento para infecções causadas por isolados de P. aeruginosa e Acinetobacter baumannii MDR e produtores de MbL. A detecção desses microrganismos é de grande importância para as comissões de controle de infecção hospitalar com o objetivo de prevenir surtos, bem como orientar a equipe médica sobre a conduta terapêutica, uma vez que há poucos antimicrobianos efetivos clinicamente para esses patógenos e as perspectivas para o desenvolvimento de novos antimicrobianos em um futuro próximo são mínimas.
7
Makena, Anne. "Structural and biochemical characterisation of bacterial metallo-β-lactamases." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:c6129257-5d92-4dd3-9a47-d0dbbcb361d9.
Full textAbstract:
One of the most prominent ways by which bacteria develop resistance to the widely used β-lactam antibiotics is by production of β-lactamases. Metallo-β-lactamases (MBLs) in particular pose an increasing public health risk due to the wide dissemination and broad substrate profile. The successful development of novel MBL inhibitors for clinical use is also dependent on sufficient understanding of the structural and functional properties of the target MBLs. From a medicinal chemistry point of view, the combination of biological diversity and structural similarity of MBLs presents a rather challenging task for the development of selective small molecules for inhibitors for bacterial MBLs. The progress made in this quest thus far is discussed at length in the introduction (Chapter 1). Robust and affordable high throughput screening platforms are indispensable in drug development. Chapter 2 of the thesis describes the identification of a novel cephalosporinbased substrates, CLS405, for MBL activity and inhibition assays. The CLS405-based assay is used in an exemplary screening of potential MBL inhibitors, resulting in the identification of N-hydroxythiazoles as novel MBL inhibitor scaffolds. An umbelliferone-derived cephalosporin substrate (FC-5) is also investigated for application in screening of MBL activity in vivo. Clinically useful MBL inhibitors must have a sufficient breadth of selectivity against multiple variants MBLs; this is particularly challenging due to the rapid MBL evolution. In Chapters 3 and 4, comparative studies of the activity, stability and structural properties of some of the clinically reported variants of the New Delhi metallo-β-lactamases (NDMs) are described. Nominal differences are noted in the kinetic parameters of the recombinant proteins, except for the apparent substrate inhibition observed with nitrocefin for variants containing the M154L substitution. Further investigations reveal significant differences in thermal stability of the NDM variants with the double mutants (NDM-5, NDM-7, NDM-8 and NDM-12) being the most stable variants, suggesting that protein stability may be a driver of MBL evolution. The Verona imipenemase metallo-β-lactamases (VIM) enzymes are among the most widely distributed MBLs with >40 variants reported (Chapter 5). Comparative studies on the biochemical and biophysical properties were carried out for five VIM variants: VIM-1, VIM- 2, VIM-4, VIM-5 and VIM-38. Clear differences in the thermal stabilities of the variants are observed, despite their similar β-lactamase activities, as previously shown for NDM variants. Interestingly, the variants show marked differences in the inhibition profile, with isoquionolone-based inhibitors selectively inhibiting VIM-5 and VIM-38 compared to VIM-1 and VIM-2. Overall, the work supports the proposal that protein stability may be an important factor in MBL evolution. Crucially, the study highlights the importance of screening MBL variants during inhibitor development programs.
8
Keshri, Vivek. "Evolutionary analysis of the β-lactamase families." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0250.
Full textAbstract:
Les antibiotiques β-lactamines sont parmi les médicaments antimicrobiens les plus anciens et les plus utilisés. L'enzyme bactérienne β-lactamase hydrolyse l'antibiotique β-lactame en cassant la structure de base "anneau β-lactame". Pour identifier les nouvelles β-lactamases, une étude complète a été réalisée dans diverses bases de données biologiques telles que Human Microbiome Project, env_nr et NCBI nr. L'analyse a révélé que les séquences ancestrales putatives et les recherches de profil HMM jouaient un rôle important dans l'identification de la base de données homologue et métagénomique à distance dans l'enzyme β-lactamase existante comme matière noire. Les larges analyses phylogénétiques des β-lactamases existantes et nouvellement identifiées représentent les nouveaux clades dans les arbres. En outre, l'activité d'hydrolyse des antibiotiques β-lactamines de séquences nouvellement identifiées (provenant d'archées et d'humains) a été étudiée en laboratoire, ce qui montre l'activité de la β-lactamase. La deuxième phase de l'étude a été entreprise pour examiner l'évolution fonctionnelle des β-lactamases. Premièrement, des séquences de protéines ß-lactamase 1155 ont été extraites de la base de données ARG-ANNOT et des valeurs CMI la littérature correspondante. Les résultats ont révélé que l'activité fonctionnelle de la β-lactamase évoluait de manière convergente au sein de la classe moléculaire. La troisième phase de cette thèse représente le développement d'une base de données intégrative de β-lactamases. La base de données publique actuelle de β-lactamases a des informations limitées, par conséquence, une base de données intégrative a été développéeThe β-lactam antibiotics are one of the oldest and widely used antimicrobial drugs. The bacterial enzyme β-lactamase hydrolyzes the β-lactam antibiotic by breaking the core structure “β-lactam ring”. To identify the novel β-lactamases a comprehensive investigation was performed in different biological databases such as Human Microbiome Project, env_nr, and NCBI nr. The analysis revealed that putative ancestral sequences and HMM profile searches played a significant role in the identification of remote homologous and uncovered the existing β-lactamase enzyme in the metagenomic database as dark-matter. The comprehensive phylogenetic analyses of extant and newly identified β-lactamase represent the novel clades in the trees. Further, the β-lactam antibiotic hydrolysis activity of newly identified sequences (from archaea and human) was investigated in laboratory, which shows β-lactamase activity.The second phase of the investigation was undertaken to examine the functional evolution of β-lactamases. First, 1155 β-lactamase protein sequences were retrieved from ARG-ANNOT database and MIC values from the corresponding literature. The results revealed that the functional activity of β-lactamase evolved convergently within the molecular class.The third phase of this thesis presents development of an integrative β-lactamase database. The existing public database of β-lactamase has limited information, therefore, an integrative database was developed
9
Bellais, Samuel. "β-lactamases à large spectre chez les flavobacteriaceae et résistance naturelle aux β-lactamines." Paris 11, 2002. http://www.theses.fr/2002PA114805.
Full text
10
Arlet, Guillaume. "Bêta-lactamases à spectre élargi : découverte et analyse épidémiologique." Paris 11, 1992. http://www.theses.fr/1992PA114835.
Full textBooks on the topic "Β-lactamases"
1
Banik, Bimal K. β-Lactams: Unique Structures of Distinction for Novel Molecules. Springer, 2012.
Find full text
2
Soulsby, Lord. Antimicrobial resistance: animal use of antibiotics. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198570028.003.0005.
Full textAbstract:
The evolution of resistance to microbes is one of the most significant problems in modern medicine, posing serious threats to human and animal health. The early work on the use of antibiotics to bacterial infections gave much hope that infectious diseases were no longer a problem, especially in the human field. However, as their use, indeed over use, progressed, resistance (both mono-resistance and multi-resistance), which was often transferable between different strains and species of bacteria, emerged. In addition, the situation is increasingly complex, as various mechanisms of resistance, including a wide range of β -lactamases, are now complicating the issue. The use of antibiotics in animals, especially those used for growth promotion, has come in for serious criticism, especially those where their use should be reserved for difficult human infections. To lend control, certain antibiotic growth promoters have been banned from use in the EU and the UK.It is now a decade since the UK House of Lords Science and Technology Committee (1998) highlighted concerns about antimicrobial resistance and the dangers to human health of resistant organisms derived from animals fed antibiotics for growth promotion or the treatment of infectious diseases. The concern expressed in the House of Lords report was similar to that in other major reports on the subject, for example from the World Health Organization, the Wellcome Foundation, the Advisory Committee on the Microbiological Safety of Food and the Swann Report (1969) in which it was recommended that antibiotics used in human medicine should not be used as growth promoters in animals. At the press conference to launch the Lord’s Report it was emphasized that unless serious attention was given to dealing with resistance ‘we may find ourselves returning to a pre-antibiotic era’. The evolution of resistance is one of the significant problems in modern medicine, a much changed situation when the early work on antibiotics gave hope that infectious diseases were no longer a problem, especially in the human field. Optimism was so strong that the Surgeon General of the USA, William H Stewart, in 1969 advised the US Congress that ‘it is time to close the book on infectious diseases and to declare that work against the pestilence is over’. This comment was not only mistaken but it was also damaging to human health undertakings and also reduced funding for research on infectious diseases.Despite the widespread support for and dependence on antibiotics, resistance was increasingly reported worldwide and to recognize the global problem a group of medical workers established in 1981, at Tufts University, the Alliance for the Prudent use of Antibiotics (APUA). This now has affiliated chapters on over 60 countries, many in the developing world. APUA claims to be the ‘world’s leading organization conducting antimicrobial resistance research, education, capacity building and advocacy at the global and grass roots levels’.
Book chapters on the topic "Β-lactamases"
1
Ronni Mol, P., Ganesan Shanthi, Ali Al-Mahmeed, Khalid M. Bindayna, and Mohammad Shahid. "Class C type β-lactamases (AmpC β-lactamases)." In Beta-Lactam Resistance in Gram-Negative Bacteria, 93–123. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-9097-6_6.
Full text
2
Danel, Franck, Malcolm G. P. Page, and David M. Livermore. "Class D β-Lactamases." In Enzyme-Mediated Resistance to Antibiotics, 163–94. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815615.ch11.
Full text
3
Bush, Karen, and Patricia A. Bradford. "β-Lactamases: Historical Perspectives." In Enzyme-Mediated Resistance to Antibiotics, 65–79. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815615.ch6.
Full text
4
Rossolini, Gian Maria, and Jean-Denis Docquier. "Class B β-Lactamases." In Enzyme-Mediated Resistance to Antibiotics, 115–44. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815615.ch9.
Full text
5
Bush, Karen. "The Evolution of β-Lactamases." In Ciba Foundation Symposium 207 - Antibiotic Resistance: Origins, Evolution, Selection and Spread, 152–66. Chichester, UK: John Wiley & Sons, Ltd., 2007. http://dx.doi.org/10.1002/9780470515358.ch10.
Full text
6
Singh, Anuradha, Mohammad Shahid, Hiba Sami, Mohd Shadab, and Haris M. Khan. "Class A Type Β-Lactamases." In Beta-Lactam Resistance in Gram-Negative Bacteria, 35–80. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-9097-6_4.
Full text
7
Meroueh, Samy O., Jooyoung Cha, and Shahriar Mobashery. "Inhibition of Class A β-Lactamases." In Enzyme-Mediated Resistance to Antibiotics, 101–14. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815615.ch8.
Full text
8
Woodford, Neil. "Rapid Characterization of β-Lactamases by Multiplex PCR." In Methods in Molecular Biology, 181–92. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60327-279-7_14.
Full text
9
Matagne, André, Moreno Galleni, Nezha Laraki, Gianfranco Amicosante, Gianmaria Rossolini, and Jean-Marie Frère. "β-Lactamases, an Old but Ever Renascent Problem." In Novel Frontiers in the Production of Compounds for Biomedical Use, 117–29. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/0-306-46885-9_7.
Full text
10
Bush, Karen, and Shahriar Mobashery. "How β-Lactamases Have Driven Pharmaceutical Drug Discovery." In Resolving the Antibiotic Paradox, 71–98. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-4897-3_5.
Full textConference papers on the topic "Β-lactamases"
1
K. Alkhudhairy, Miaad, and Mahasin Sifir Madkhur. "Detection of Proteus Mirabilis Carrying blaCTX-M, blaSHV, and blaTEM Genes Related to Urinary Tract Infections." In IX. International Scientific Congress of Pure, Applied and Technological Sciences. Rimar Academy, 2023. http://dx.doi.org/10.47832/minarcongress9-4.
Full textAbstract:
Background: Proteus mirabilis is a bacterium that causes many serious systematic infections. The aim of the study: Determination of Proteus mirabilis carrying blaCTX-M, blaSHV, and blaTEM genes related to urinary tract infections. Materials and Methods: 402 samples of urine were randomly collected from patients with symptomatic urinary tract infections at Al-Sadder Hospital in Al-Najaf Governorate, Iraq, from October 2022 to December 2023. Results: 71 (17.7%) isolates of P. mirabilis were identified according to microscopic, culture, and biochemical characteristics, then were tested for their ability to produce extended-spectrum β-lactamases by the two phenotypic methods: double disc synergy test and modified Hodge test. 19 (26.8%) extended-spectrum β-lactamases-producers, which had previously been evaluated using the phenotypic method, were subjected to the investigation of β-lactamases encoding genes by using the polymerase chain reaction technique. This molecular technique detected 8 (42.1%) isolates carrying single β-lactamases encoding gene, 7 (36.8%) isolates had blaCTX-M gene, only one isolate (5.3%) carried blaSHV gene, and no single blaTEM gene was detected in any isolate. 3 (15.8%) isolates harbored multiple genes: blaCTX-M and blaTEM. Conclusions: blaCTX-M gene was found to be more predominant among the extended-spectrum β-lactamases-producer under study than other genes
2
Rosa, BKV, and B. Guedin. "PREVALÊNCIA DE MICRORGANISMOS PRODUTORES DE CARBAPENEMASES EM PACIENTES AMBULATORIAIS NA REGIÃO METROPOLITANA DE PORTO ALEGRE NO ANO DE 2022." In Resumos do 55º Congresso Brasileiro de Patologia Clínica/Medicina Laboratorial, 63. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s2.9698.
Full textAbstract:
Objetivo: As infecções do trato urinário (ITUs) estão entre as causas mais comuns de busca por atendimento em serviços de saúde em uma ampla faixa etária. São causadas principalmente por enterobactérias e possuem crescente perfil de resistência aos antimicrobianos ao longo dos anos. Bactérias produtoras de carbapenemases são consideradas emergentes, particularmente serino betalactamases (KPC) e metalo-β-lactamases. O objetivo deste estudo foi identificar a prevalência de microrganismos produtores dessas carbapenemases por meio de teste fenotípico por Blue Carba em uroculturas de pacientes ambulatoriais da região metropolitana de Porto Alegre no ano de 2022. Método: Foi realizado um estudo transversal através de banco de dados provenientes de um laboratório referência da região. Totalizaram-se 187 uroculturas com microrganismos produtores de carbapenemases, dentre elas, 135 produtoras de KPC e 52 produtoras de metalo-β-lactamases, prevalecendo entre os grupos a bactéria Klebsiella pneumoniae com 94,07% e 57,69%, respectivamente. Conclusão: Salienta-se a necessidade de investigações para a definição de um perfil microbiológico que difere do de outras regiões pelas peculiaridades de cada localidade, buscando políticas públicas voltadas para a prevenção das ITUs e a conscientização da população quanto ao uso indiscriminado de antibióticos.
3
Jeong, Seok Hoon, Il Kwon Bae, Seung Ghyu Sohn, Ha Il Jung, Young Jun An, Eui Suk Sohn, Jung Hun Lee, and Sang Hee Lee. "Characterization and molecular epidemiology of Enterobacter cloacae clinical isolates producing extended-spectrum β-lactamases." In Proceedings of the II International Conference on Environmental, Industrial and Applied Microbiology (BioMicroWorld2007). WORLD SCIENTIFIC, 2009. http://dx.doi.org/10.1142/9789812837554_0101.
Full text
4
K. Alkhudhairy, Miaad, and Elhassan Benyagoub. "Frequency of Genes Mediated β-lactams Resistance in Acinetobacter Baumannii Isolates from Iraq." In X INTERNATIONAL CONGRESS OF PURE AND APPLIED TECHNOLOGICAL SCIENCES. Rimar Academy, 2023. http://dx.doi.org/10.47832/minarcongress10-2.
Full textAbstract:
Background: Acinetobacter baumannii is a nosocomial virulent microorganism that can cause acute and chronic infections in burn patients. The aim of the study: Diagnosis of genes mediated β-lactams resistance among test isolates. Materials and Methods: 649 swabs collected from inpatients with burn-wound infections at a burn center in Al-Najaf Province/ Iraq, from August 2022 to February 2023. Results: 68/ 649 (10.5%) isolates of Acinetobacter baumannii were identified according to microscopically, cultural, and biochemical features. 22 (32.4%) isolates were found able to produce extended-spectrum β-lactamases by using the double disks synergy method, and these producers tested by polymerase chain reactions technique for molecular determination β-lactams resistance encoding genes. This technique determined that the frequency of a single blaTEM gene and a single blaCTXM gene was 3/ 22 (13.6%) for each one among the test isolates and that 9/ 22 (41%) isolates possessed linked genes: the blaCTXM and blaTEM genes, whereas the blaSHV gene was not identified in any test isolate. Conclusions: The co-associated (blaTEM and blaCTXM) genes were revealed to be prevalent among the test isolates
5
Rath, Soumya Lipsa, Smaranika Mohapatra, and Veena Gayathri. "Identifying Antibiotic-Resistant Mutants in β-Lactamases for Class A and Class B Using Unsupervised Machine Learning." In RAiSE-2023. Basel Switzerland: MDPI, 2024. http://dx.doi.org/10.3390/engproc2023059146.
Full text
6
"Molecular composition - inhibition activity relationships for humic substances narrow fractions sets obtained by solid-phase extraction." In Sixth International Conference on Humic Innovative Technologies "Humic Substances and Eco-Adaptive Technologies ”(HIT – 2021). Non-Commercial Partnership "Center for Biogenic Resources "Humus Sapiens" (NP CBR "Humus Sapiens"), 2021. http://dx.doi.org/10.36291/hit.2021.mikhnevich.001.
Full textAbstract:
Humic substances (HS) have a wide spectrum of biological activity including inhibitory activity against β-lactamases.1 The latter are capable of hydrolyzing beta-lactam antibiotics and represent one of the main pathways of bacterial antibiotic resistance. HS are characterized by low toxicity and good solubility in water. A use of HS for therapeutic purposes is hindered by extreme molecular heterogeneity and high level of isomeric complexity. Solid-phase extraction (SPE) fractionation in combination with ultra-high resolution mass spectrometry (FTICR MS) is a promising method to simplify this molecular system and isolate the most active components of HS. The aim of this work was to test various SPE fractionation schemes as an approach to directed isolation of the components with the given activity from HS. The sample of coal humic acids (CHA-G) was isolated from the commercial sodium humate “Genesis” and separated using SPE cartridge according to gradients in polarity1 and acidity2 inherent within the molecular components of HS. Inhibitory activity against β- lactamase TEM-1 and its mutants was measured using chromogenic substrate CENTA. Molecular composition of fractions was determined using FTICR mass spectrometer 15 T solariX (Bruker Daltonics) located at the Collective Use Center of Zelinsky Institute of Organic Chemistry of RAS. Molecular assignments were plotted into van Krevelen diagrams. The diagrams were binned into 20 cells are assigned to seven chemotypes, and occupational densities for each chemotype were calculated after Perminova.3 For the fractions separated by polarity, a substantial difference in the molecular composition was observed. Inhibitory activity grew along with an increase in hydrophobicity. The HS activity increased along with an increase in contribution of condensed tannins and phenylisopropanoids (O/C <0.5, H/C <1.4) and decreased along with contribution of hydrolyzed tannins (O/C> 0.5, H/C <1.4). The similar analysis was conducted for the fractions separated with regard to pKa value of the dominating functional groups. The most isomeric complex molecular components were defined, which can be found in different HS fractions, but they are identical in elemental composition. The data obtained make it possible to choose the most efficient fractionation method that effectively lowers the molecular complexity of HS and makes it possible to isolate the most active HS fractions. SPE-fractionation in combination with 2D chromatography is going to be used in our future studies to achieve high resolution separation and more reliable “molecular composition-activity” relationships. Further research might bring substantial advance in the field of directed design of biologically active humic-based materials and compositions. Acknowledgements. This work was supported by the grant of the Russian Science Foundation no 21-73-20202. The center of collective use of the Zelinsky IOC RAS is appreciated. The research was conducted in the framework of the Scientific-Educational School of the Lomonosov MSU “Future of the plant and global environmental change”. References 1. Mikhnevich et al., ACS Omega, 2021, https://doi.org/10.1021/acsomega.1c02841 2. Zherebker et al., Environ. Sci. Technol. 2020, 54, 2667−2677 3. Perminova, I. V. PAC, 2019, 91(5), 851
7
Vasić, Katja, Mateja Primožič, Mislav Trbušić, Viktor Goričan, Marko Jesenik, Anton Hamler, Željko Knez, Yilmaz Yürekli, and Maja Leitgeb. "Magnetic Field as a Tool for Enhancing β -Lactamase Activity." In International Conference on Technologies & Business Models for Circular Economy. University of Maribor Press, 2024. http://dx.doi.org/10.18690/um.fkkt.1.2024.11.
Full textAbstract:
β-Lactam antibiotics have been extensively employed in bacterial treatment ever since penicillin's groundbreaking discovery. Despite the proliferation of antibiotics in the pharmaceutical sector today, bacteria often evolve defense mechanisms. Chief among these is the production of β-lactamase enzymes, which degrade β-lactam antibiotics, representing a prevalent form of antibiotic resistance. Additionally, these antibiotics exhibit limited biodegradability, with only 20% breaking down naturally. Hence, finding effective methods to mitigate the presence of β-lactam antibiotics is crucial in combating antibiotic pollution.
8
Rammadan ABDUL, Fatima, Ihsan Ali RAHEEEM, Alaa Laebi ABDULLAH, and Batool Abd Al Ameer BAQER. "DETECTION OF SOME VIRULENCE FACTORS AND ANTIBIOTICS RESISTANCE OF KLEBSIELLA PNEUMONIAE." In DETERMINATION OF THE ACTUAL INTENSITY BY CORRECTION OF THE EMISSION SPECTRUM LINES OF HEAVY METALS CONTAINED IN CRUDE OIL USING LASER INDUCED PLASMA –TECHNIQUE. Rimar Academy, 2022. http://dx.doi.org/10.47832/minarcongress4-9.
Full textAbstract:
Background: Infections of Klebsiella pneumoniae can include; diarrhea, septicemia, pneumonia, urinary tract infection and infections of soft tissues. Many factors are donated to K. pneumoniae pathogenicity particularly production of enzymes and formation of biofilm. Objective: find the relationship between the resistance of K. pneumoniae bacteria to antibiotics of quinolones and their ability to produce enzymes of beta lactamase. Materials and Methods: The Study included isolation and identification of (51) isolate of K. pneumoniae and (94) isolates of other bacteria from different clinical sources in some Baghdad hospitals. Results: The isolation and diagnosis of (51) isolates of K. pneumoniae from infection of urinary tract were 49.1%, infection of wounds were 31.3% and infection of burns were19.6%. All bacterial isolates were identified by the biochemical, cultural and microbial characteristics and confirmed by Api E20 System. I showed of β-lactamase test of Klebsiella pneumoniae revealed that (35) 68.6% isolates were positive. While 16 (31.4%) isolates were able to produce urease. Four groups of quinolones were tested by done the sensitivity test of isolates and results revealed the following percentage of resistant to Norfloxacin, Ofloxacin and ciprofloxacin consequently were (50.1%), (44.5%), (39.4%). whereas, the lower percent of resistant to Levofloxacin was (26.8%). In contrast, the βlactamase positive K. pneumoniae exhibited a high resistance in compare to isolates that negative for β-lactamase. The minimum inhibitory range concentrations of ciprofloxacin were arranged between (4-512 µg\ml). From isolates that resistant to Ciprofloxacin, the DNA plasmid was determined. Single plasmid bands were included in two isolates with same size and other isolates were confined free plasmid
9
Costa, Luiz, Denize Favaro, and Víctor Antunes. "In vitro penicillinase activity of β-lactamase OXA-143(P227S): pH effect." In Congresso de Iniciação Científica UNICAMP. Universidade Estadual de Campinas, 2019. http://dx.doi.org/10.20396/revpibic2720192296.
Full text
10
Lavandeira Pérez, M., E. Martínez Ruiz, G. Casarrubios Lázaro, I. Mendoza Acosta, P. Tardaguila Molina, C. Dean Barahona, Á. Yuste Gutiérrez, M. Blanco Crespo, A. Lázaro López, and AM Horta Hernández. "4CPS-249 Second generation β-lactam/β-lactamase inhibitor combinations: ceftazidime–avibactam and ceftolozane–tazobactam experience of use." In 25th Anniversary EAHP Congress, Hospital Pharmacy 5.0 – the future of patient care, 23–28 March 2021. British Medical Journal Publishing Group, 2021. http://dx.doi.org/10.1136/ejhpharm-2021-eahpconf.81.
Full textReports on the topic "Β-lactamases"
1
Cang, Huai Qin, XiangHua Quan, XiangHua Chu, Yu Liang, Xue Yang, and Jing Li. Carbapenems versus β-lactam and β-lactamase inhibitors for treatment of Nosocomial Pneumonia: a systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, April 2023. http://dx.doi.org/10.37766/inplasy2023.4.0113.
Full text
2
ยมภักดี, ชุลี, and วรินทร ชวศิริ. สารออกฤทธิ์ต้านจุลินทรีย์จากมะแขว่น Zanthoxylum limonella Alston : รายงานการวิจัยฉบับสมบูรณ์. จุฬาลงกรณ์มหาวิทยาลัย, 2011. https://doi.org/10.58837/chula.res.2011.48.
Full textAbstract:
Zanthoxylum limonella Alston หรือมะแขว่น นิยมใช้ในการปรุงแต่งรสอาหารและยังเป็นสมุนไพรตามภูมิปัญญาท้องถิ่นในประเทศไทย สำหรับการวิจัยนี้พบว่าน้ำมันหอมระเหยในมะแขว่น ตลอดจนส่วนประกอบย่อย และ สามสารหลักที่พบในน้ำมันหอมระเหยจากมะแขว่น มีฤทธิ์ในการต้านเชื้อจุลินทรีย์ได้หลายชนิด ทั้งนี้รวมไปถึงเชื้อจุลินทรีย์ที่ดื้อต่อยาปฏิชีวนะด้วย ซึ่งสามารถแยกส่วนประกอบหลักได้เป็นส่วนประกอบย่อยที่ 1 และ 2 โดยสาร Sabinene เป็นสารหลักที่พบในส่วนประกอบย่อยที่ 1 โดยพบอยู่ถึงร้อยละ 54 และพบในส่วนประกอบย่อยที่ 2 อยู่ร้อยละ 41 ซึ่งเป็นที่น่าสนใจเป็นอย่างยิ่งเนื่องจากงานวิจัยนี้พบฤทธิ์ต้านจุลินทรีย์ทั้งในกลุ่มของแบคทีเรียแกรมบวกและแกรมลบ ยกเว้นเชื้อ Pseudomonas aeruginosa จากทั้งในน้ำมันหอมระเหยและส่วนประกอบย่อยเหล่านี้ และเมื่อได้เปรียบเทียบประสิทธิภาพในการฆ่าจุลินทรีย์ พบว่าน้ำมันหอมระเหยสามารถฆ่าเชื้อจุลินทรีย์ทุกชนิดได้ดีกว่าสาร Sabinene ซึ่งสามารถบ่งชี้ได้ว่าเกิดจากการเสริมฤทธิ์กันของสารประกอบย่อยต่างๆ ที่มีอยู่ในน้ำมันหอมระเหย โดยน้ำมันหอมระเหยนี้สามารถฆ่าเชื้อ S. aureus และเชื้อ E. coli ได้อย่างสมบูรณ์ภายในเวลา 9 นาที โดยใช้ความเข้มข้นเป็น 2 เท่าของความเข้มข้นน้อยที่สุดที่ใช้ในการฆ่าเชื้อ และยังมีความสามารถในการฆ่าเชื้อดื้อยา methicillin-resistant S. aureus และเชื้อดื้อยา extended-spectrum β-lactamase-producing E. coli ได้อย่างสมบูรณ์ภายในเวลา 90 นาทีที่ค่าความเข้มข้นเท่ากัน งานวิจัยนี้เป็นงานวิจัยแรกที่ค้นพบว่าน้ำมันหอมระเหยจากผลมะแขว่นมีฤทธิ์ต่อเชื้อดื้อยาปฏิชีวนะด้วย ซึ่งสามารถนำไปประยุกต์ใช้ในการถนอมอาหาร รวมไปถึงพัฒนาเพื่อใช้ในด้านการแพทย์เพื่อลดปัญหาการแพร่ระบาดของเชื้อดื้อยาในปัจจุบัน
3
Zhou, Yiwu. Early prediction models for Extended-spectrum β-lactamase-producing Escherichia coli infection in emergency department: A protocol for systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, March 2021. http://dx.doi.org/10.37766/inplasy2021.3.0049.
Full text