Journal articles: 'Rv0805 - Mycobacterium Tuberculosis'

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Shenoy, Avinash R., Maja Capuder, Petra Draškovič, Doriano Lamba, Sandhya S. Visweswariah, and Marjetka Podobnik. "Structural and Biochemical Analysis of the Rv0805 Cyclic Nucleotide Phosphodiesterase from Mycobacterium tuberculosis." Journal of Molecular Biology 365, no. 1 (January 2007): 211–25. http://dx.doi.org/10.1016/j.jmb.2006.10.005.

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Arora, Simran Kaur, Anwar Alam, Javeed Ahmad, Nilofer Naqvi, Seyed Ehtesham Hasnain, and Nasreen Zafar Ehtesham. "Role of Mycobacterium tuberculosis expressing unique protein Rv000B in immune modulation of host cell machinery." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 120.7. http://dx.doi.org/10.4049/jimmunol.202.supp.120.7.

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Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb.), an intracellular pathogen remains a major global health problem. M.tb., comprising more than 120 species has evolved by successive genomic reduction events. Comparative genomic and proteomic analysis of 13 Mycobacterium species classified into Strict pathogens (virulent), Opportunistic pathogens (Non-tuberculous Mycobacteria, NTM) and the Non-pathogenic bacteria revealed the presence of 25 unique protein. These 25 proteins share less than 20% homology with any other proteins of Mycobacteria species used in the study. Rv000B, one of the unique proteins is present in M.tb and M. bovis BCG only. The presence of Rv000B in M. tb and M.bovis BCG only points to its importance as “Signature proteins”, suggesting that Rv000B could be used for its diagnostic potential. Rv000B is a hypothetical protein and hence it will be interesting to study their functional role in the pathogenesis of M.tb. In-silico analysis of Rv000B revealed that this protein is highly disordered and unstable. Immunogenicity of Rv000B protein was evaluated by treating the splenocytes ex-vivo obtained from mice that were previously immunized with Rv000B protein. Our results showed that Rv000B is highly antigenic and elicited a pro-inflammatory immune response. High IgG reactivity of Rv000B is also seen in immunized mice and different categories of TB patients. Besides inducing Th1 responses, it also significantly induced apoptosis of macrophages. Therefore, these pro-host antigenic proteins are ideal candidates to produce recombinant BCG vaccine to enhances its vaccine potential.

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Goldstone, Rachael M., Sunali D. Goonesekera, Barry R. Bloom, and Samantha L. Sampson. "The Transcriptional Regulator Rv0485 Modulates the Expression of a pe and ppe Gene Pair and Is Required for Mycobacterium tuberculosis Virulence." Infection and Immunity 77, no. 10 (August 3, 2009): 4654–67. http://dx.doi.org/10.1128/iai.01495-08.

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ABSTRACT The pe and ppe genes are unique to mycobacteria and are widely speculated to play a role in tuberculosis pathogenesis. However, little is known about how expression of these genes is controlled. Elucidating the regulatory control of genes found exclusively in mycobacteria, such as the pe and ppe gene families, may be key to understanding the success of this pathogen. In this study, we used a transposon mutagenesis approach to elucidate pe and ppe regulation. This resulted in the identification of Rv0485, a previously uncharacterized transcriptional regulator. Microarray and quantitative real-time PCR analysis confirmed that disruption of Rv0485 reduced the expression of the pe13 and ppe18 gene pair (Rv1195 and Rv1196), defined the Rv0485 regulon, and emphasized the lack of global regulation of pe and ppe genes. The in vivo phenotype of the Rv0485 transposon mutant strain (Rv0485::Tn) was investigated in the mouse model, where it was demonstrated that the mutation has minimal effect on bacterial organ burden. Despite this, disruption of Rv0485 allowed mice to survive for significantly longer, with substantially reduced lung pathology in comparison with mice infected with wild-type Mycobacterium tuberculosis. Infection of immune-deficient SCID mice with the Rv0485::Tn strain also resulted in extended survival times, suggesting that Rv0485 plays a role in modulation of innate immune responses. This is further supported by the finding that disruption of Rv0485 resulted in reduced secretion of proinflammatory cytokines by infected murine macrophages. In summary, we have demonstrated that disruption of a previously uncharacterized transcriptional regulator, Rv0485, results in reduced expression of pe13 and ppe18 and attenuation of M. tuberculosis virulence.

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Srivastava, Ranjana, D. Kumar, M. N. Waskar, Meera Sharma, V. M. Katoch, and Brahm S. Srivastava. "Identification of a repetitive sequence belonging to a PPE gene of Mycobacterium tuberculosis and its use in diagnosis of tuberculosis." Journal of Medical Microbiology 55, no. 8 (August 1, 2006): 1071–77. http://dx.doi.org/10.1099/jmm.0.46379-0.

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A repetitive sequence specific to Mycobacterium tuberculosis was isolated from a λgt11 library of M. tuberculosis by DNA–DNA hybridization using genomic DNA of M. tuberculosis as probe followed by subtractive hybridization with a cocktail of other mycobacterial DNA. This led to identification of CD192, a 1291 bp fragment of M. tuberculosis containing repetitive sequences, which produced positive hybridization signals with M. tuberculosis DNA within 30 min. Nucleotide sequencing revealed the presence of several direct and inverted repeats within the 1291 bp fragment that belonged to a PPE family gene (Rv0355) of M. tuberculosis. The use of CD192 as a DNA probe for the identification of M. tuberculosis in culture and clinical samples was investigated. The 1291 bp sequence was present in M. tuberculosis, Mycobacterium bovis and M. bovis BCG, but was not present in many of the other mycobacterial strains tested, including M. tuberculosis H37Ra. More than 300 clinical isolates of M. tuberculosis were probed with CD192, and the presence of the 1291 bp sequence was observed in all the clinical strains, including those lacking IS6110. The sequence displayed RFLP among the clinical isolates. A PCR assay was developed which detected M. tuberculosis with 100 % specificity from specimens of sputum, cerebrospinal fluid and pleural effusion from clinically diagnosed cases of tuberculosis.

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Slizen, V. V., L. K. Surkova, and G. L. Gurevich. "Variability assessment of PE_PGRS genes and DNA repair, replication, and recombination genes in Mycobacterium tuberculosis." Proceedings of the National Academy of Sciences of Belarus, Medical series 20, no. 1 (March 2, 2023): 42–57. http://dx.doi.org/10.29235/1814-6023-2023-20-1-42-57.

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The variability assessment of PE/PPE genes, as well as of DNA repair, replication, and recombination system genes may drive the concept of mechanisms of Mycobacterium tuberculosis evolution and adaptation.The aim is to study the variability of PE_PGRS genes, 3R-system genes (DNA repair, recombination, and replication) to assess the mechanisms of evolutionary changes in M. tuberculosis.Whole genome sequencing of M. tuberculosis 11502 (the Beijing genotype subtype B0/W148 cluster 100-32), M. tuberculosis 5005 (the Beijing genotype subtype B0/W148), M. tuberculosis 4860 (the LAM genotype) strains was performed. They were isolated from patients with newly diagnosed pulmonary tuberculosis. Genomes were uploaded to the GanBank, NCBI: M. tuberculosis 11502 – access code: CP070338.1, M. tuberculosis 5005 – access code: CP053092.1, M. tuberculosis 4860 – access code: CP049108.1. A reference genome (M. tuberculosis H37Rv; NC_000962.3) was used for genetic analysis. In the M. tuberculosis 11502 genome, 44.4 ± 6.8 % of genes (24 genes out of 54) were revealed in the mutations related to the 3R system, while in M. tuberculosis 4860– 29.6 ± 6.2 % (16 genes out of 54). In the 3R system genes, a slight shift of mutations towards replacement by adenine and thymine was revealed, while the entire genome of M. tuberculosis 11502 (compared to M. tuberculosis H37Rv) demonstrated mutations, resulting in a slight accumulation of G + C. Mutations in the 3R system genes may lead to the suboptimal activity of proteins responsible for the DNA-repair, resulting in the upsurge of mutation frequency and promoting adaptive evolution. PE_PGRS genes in the genome of M. tuberculosis 11502, 4860, and 5005 exhibited a high variability and their variability diverged among different members of this gene family. A high level of tetranucleotides CGGC was found in the majority of PE_PGRS family genes, where their proportion varied from 2.11 to 8.42 %, while an average proportion of CGGC in the M. tuberculosis genome was 1.62 %. Some genes in the M. tuberculosis genome were detected to carry no tetranucleotides CGGC (Rv0011, Rv0100, Rv0460, Rv0616A, Rv0691A, Rv0722, Rv0863, Rv0909, Rv1038c, Rv1197, Rv2347c, Rv2452c, and Rv3330c). The DNA conformation analysis at the mutation sites in the genes, associated with resistance to anti-tuberculosis drugs, showed that the secondary DNA structures were mainly formed by nucleotides CGGC, GCGC, GGG, GGGG, CTGC, and mutations occurred, predominantly, at the sites of forming secondary DNA structures (hairpins) where the redistribution of energy and charges can influence the accuracy of replication and result in replication errors and a mutation event. A number of additional factors can influence the probability of a mutation event. These are the factors that can neutralize the energy changes in the DNA secondary structures, and can affect the accuracy of DNA-repair and replication (mutations in the gyrA gene, in the 3R-system genes).

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Ali, Md Kaisar, Lambert Nzungize, Khushnood Abbas, Nzaou Stech Anomene Eckzechel, M. A. Abo-kadoum, Ulrich Aymard Ekomi Moure, Mohammed Asaad, Aftab Alam, Junqi Xu, and Jianping Xie. "Mycobacterium tuberculosis Rv0580c Impedes the Intracellular Survival of Recombinant Mycobacteria, Manipulates the Cytokines, and Induces ER Stress and Apoptosis in Host Macrophages via NF-κB and p38/JNK Signaling." Pathogens 10, no. 2 (February 1, 2021): 143. http://dx.doi.org/10.3390/pathogens10020143.

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The Mycobacterium tuberculosis (M. tb) genome encodes a large number of hypothetical proteins, which need to investigate their role in physiology, virulence, pathogenesis, and host interaction. To explore the role of hypothetical protein Rv0580c, we constructed the recombinant Mycobacterium smegmatis (M. smegmatis) strain, which expressed the Rv0580c protein heterologously. We observed that Rv0580c expressing M. smegmatis strain (Ms_Rv0580c) altered the colony morphology and increased the cell wall permeability, leading to this recombinant strain becoming susceptible to acidic stress, oxidative stress, cell wall-perturbing stress, and multiple antibiotics. The intracellular survival of Ms_Rv0580c was reduced in THP-1 macrophages. Ms_Rv0580c up-regulated the IFN-γ expression via NF-κB and JNK signaling, and down-regulated IL-10 expression via NF-κB signaling in THP-1 macrophages as compared to control. Moreover, Ms_Rv0580c up-regulated the expression of HIF-1α and ER stress marker genes via the NF-κB/JNK axis and JNK/p38 axis, respectively, and boosted the mitochondria-independent apoptosis in macrophages, which might be lead to eliminate the intracellular bacilli. This study explores the crucial role of Rv0580c protein in the physiology and novel host-pathogen interactions of mycobacteria.

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Grosse-Siestrup, Benjamin T., Tuhina Gupta, Shelly Helms, Samantha L. Tucker, Martin I. Voskuil, Frederick D. Quinn, and Russell K. Karls. "A Role for Mycobacterium tuberculosis Sigma Factor C in Copper Nutritional Immunity." International Journal of Molecular Sciences 22, no. 4 (February 20, 2021): 2118. http://dx.doi.org/10.3390/ijms22042118.

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Sigma factor C (SigC) contributes to Mycobacterium tuberculosis virulence in various animal models, but the stress response coordinated by this transcription factor was undefined. The results presented here indicate that SigC prevents copper starvation. Whole genome expression studies demonstrate short-term (4-h) induction of sigC, controlled from a tetracycline-inducible promoter, upregulates ctpB and genes in the nonribosomal peptide synthase (nrp) operon. These genes are expressed at higher levels after 48-h sigC induction, but also elevated are genes encoding copper-responsive regulator RicR and RicR-regulated copper toxicity response operon genes rv0846–rv0850, suggesting prolonged sigC induction results in excessive copper uptake. No growth and global transcriptional differences are observed between a sigC null mutant relative to its parent strain in 7H9 medium. In a copper-deficient medium, however, growth of the sigC deletion strain lags the parent, and 40 genes (including those in the nrp operon) are differentially expressed. Copper supplementation reverses the growth defect and silences most transcriptional differences. Together, these data support SigC as a transcriptional regulator of copper acquisition when the metal is scarce. Attenuation of sigC mutants in severe combined immunodeficient mice is consistent with an inability to overcome innate host defenses that sequester copper ions to deprive invading microbes of this essential micronutrient.

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Bondoc, Jasper Marc G., Hiten J. Gutka, Mashal M. Almutairi, Ryan Patwell, Maxwell W. Rutter, Nina M. Wolf, Ram Samudrala, Shahila Mehboob, and Farahnaz Movahedzadeh. "Rv0100, a proposed acyl carrier protein in Mycobacterium tuberculosis: expression, purification and crystallization." Acta Crystallographica Section F Structural Biology Communications 75, no. 10 (September 24, 2019): 646–51. http://dx.doi.org/10.1107/s2053230x19012652.

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Acyl carrier proteins (ACPs) are important components in fatty-acid biosynthesis in prokaryotes. Rv0100 is predicted to be an essential ACP in Mycobacterium tuberculosis, the pathogen that is the causative agent of tuberculosis, and therefore has the potential to be a novel antituberculosis drug target. Here, the successful cloning and purification of Rv0100 using Mycobacterium smegmatis as a host is reported. Crystals of the purified protein were obtained that diffracted to a resolution of 1.9 Å. Overall, this work lays the foundation for the future pursuit of drug discovery and development against this potentially novel drug target.

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Kovács, L., Ágnes Csanádi, Éva Kiss, and A. Miczak. "Rv0802c Acetyltransferase from Mycobacterium tuberculosis H37Rv." Acta Microbiologica et Immunologica Hungarica 52, no. 3-4 (October 1, 2005): 363–71. http://dx.doi.org/10.1556/amicr.52.2005.3-4.8.

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Payros, Delphine, Henar Alonso, Wladimir Malaga, Arnaud Volle, Serge Mazères, Sébastien Déjean, Sophie Valière, et al. "Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages." PLOS Pathogens 17, no. 11 (November 1, 2021): e1010020. http://dx.doi.org/10.1371/journal.ppat.1010020.

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Mycobacterium tuberculosis, the main causative agent of human tuberculosis, is transmitted from person to person via small droplets containing very few bacteria. Optimizing the chance to seed in the lungs is therefore a major adaptation to favor survival and dissemination in the human population. Here we used TnSeq to identify genes important for the early events leading to bacterial seeding in the lungs. Beside several genes encoding known virulence factors, we found three new candidates not previously described: rv0180c, rv1779c and rv1592c. We focused on the gene, rv0180c, of unknown function. First, we found that deletion of rv0180c in M. tuberculosis substantially reduced the initiation of infection in the lungs of mice. Next, we established that Rv0180c enhances entry into macrophages through the use of complement-receptor 3 (CR3), a major phagocytic receptor for M. tuberculosis. Silencing CR3 or blocking the CR3 lectin site abolished the difference in entry between the wild-type parental strain and the Δrv0180c::km mutant. However, we detected no difference in the production of both CR3-known carbohydrate ligands (glucan, arabinomannan, mannan), CR3-modulating lipids (phthiocerol dimycocerosate), or proteins in the capsule of the Δrv0180c::km mutant in comparison to the wild-type or complemented strains. By contrast, we established that Rv0180c contributes to the functionality of the bacterial cell envelope regarding resistance to toxic molecule attack and cell shape. This alteration of bacterial shape could impair the engagement of membrane receptors that M. tuberculosis uses to invade host cells, and open a new perspective on the modulation of bacterial infectivity.

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He, H., D. J. Bretl, R. M. Penoske, D. M. Anderson, and T. C. Zahrt. "Components of the Rv0081-Rv0088 Locus, Which Encodes a Predicted Formate Hydrogenlyase Complex, Are Coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis." Journal of Bacteriology 193, no. 19 (August 5, 2011): 5105–18. http://dx.doi.org/10.1128/jb.05562-11.

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Yu, Xia, Guirong Wang, Suting Chen, Guomei Wei, Yuanyuan Shang, Lingling Dong, Thomas Schön, et al. "Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin." Antimicrobial Agents and Chemotherapy 60, no. 9 (June 20, 2016): 5232–37. http://dx.doi.org/10.1128/aac.00393-16.

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ABSTRACTAntofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying itsin vitroactivity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinicalMycobacterium tuberculosisstrains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions ofgyrA(Rv0006) andgyrB(Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wild-type strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective.

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Dong, Shishang, Zhenzhen Ding, Yu Wang, Yan Yang, Yonghong Mao, and Ying Wang. "Transcription factor Rv0081 fromMycobacterium tuberculosis: purification, crystallization and initial crystallographic analysis." Acta Crystallographica Section F Structural Biology Communications 73, no. 5 (April 26, 2017): 281–85. http://dx.doi.org/10.1107/s2053230x17005064.

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Because of its high infectivity and pathogenicity,Mycobacterium tuberculosisis a serious threat to human health. While the transcription-regulatory system ofM. tuberculosisremains incompletely understood, Rv0081, an essential regulatory hub, is known to mediate the initial response to hypoxia in the long-term survival ofM. tuberculosis. Here, the production, crystallization and initial X-ray crystallographic analysis of Rv0081 are reported. The crystals of Rv0081 belonged to space groupP62, with unit-cell parametersa= 67.48,b = 67.48,c = 40.84 Å, γ = 120°. The Matthews coefficient is 2.09 Å3 Da−1, assuming the presence of one molecule in the asymmetric unit, with a corresponding solvent content of 41.27%. Phasing of the native crystal form of Rv0081 was performed by molecular replacement. Currently, the structure has been refined to 2.00 Å resolution with anRworkof 25.99% and anRfreeof 30.88%.

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Авдиенко, Вадим Григорьевич, Ирина Юрьевна Андриевская, Ирина Вячеславовна Козлова, Сурен Суренович Бабаян, Татьяна Геннадьевна Смирнова, Елена Евгеньевна Ларионова, Лариса Николаевна Черноусова, and Владислав Яковлевич Гергерт. "ДИАГНОСТИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ДВУСАЙТОВОГО ИФА С МОНОКЛОНАЛЬНЫМИ АНТИТЕЛАМИ ДЛЯ ВЫЯВЛЕНИЯ МИКОБАКТЕРИАЛЬНЫХ АНТИГЕНОВ ПРИ КУЛЬТИВИРОВАНИИ МАТЕРИАЛА ОТ БОЛЬНЫХ ТУБЕРКУЛЕЗОМ В АВТОМАТИЗИРОВАННОЙ СИСТЕМЕ ВАОТС MGIT, "Вестник Центрального научно-исследователь." Вестник ЦНИИТ, no. 4 (2018): 58–67. http://dx.doi.org/10.7868/s2587667818040088.

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На протяжении последних 20-ти лет MPT64 остается наиболее значимым антигеном микобактерий для лабораторной диагностики туберкулеза. В работе проведена оценка эффективности выявления Mycobacterium tuberculosis методом двусайтового иммуноферментного анализа (ИФА) с помощью парных моноклональных антител против ряда антигенов микобактерий: MPT63, Rv0009, LpqH, MPT83, Ag85B, pstS/phoS, PstS1. Были исследованы 224 культуры Mycobacterium tuberculosis от больных туберкулезом легких, 38 культур нетуберкулезных микобактерий и 120 культур неспецифической микрофлоры. Наибольшая диагностическая эффективность (97,35%) была показана для ИФА, выявляющего антиген MPT64, взятого как антиген сравнения. Для антигенов MPT63 (95,95%), Rv0009 (94,85%), LpqH (91,18%), MPT83 (94,23%), 24 kDa (93,33%), Ag85B (93,41%) и PstS1 (94,30%) эффективность также была достаточно высока. При этом специфичность определения антигенов MPT63 (99%) и MPT83 (98,1%) была выше, чем у антигена сравнения MPT64 (97,5%). Чувствительность диагностики по MPT64 (97,17%) была несколько ниже в сравнении с антигеном Ag85B (98,22%). Эти результаты подтверждают, что подобный ИФА, предназначенный для детекции специфических микобактериальных антигенов, имеет перспективы развития и применения как дополнительный метод при исследовании культуральных образцов диагностического материала от больных туберкулезом.

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Buckoreelall, Kajal, Yanjie Sun, Judith V. Hobrath, Landon Wilson, and William B. Parker. "Identification of Rv0535 as methylthioadenosine phosphorylase from Mycobacterium tuberculosis." Tuberculosis 92, no. 2 (March 2012): 139–47. http://dx.doi.org/10.1016/j.tube.2011.11.010.

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Teriete, Peter, Yong Yao, Adrian Kolodzik, Leigh A. Plesniak, Michael Niederweis, and Francesca M. Marassi. "Structure of the Mycobacterium Tuberculosis Virulence Factor Rv0899 (ompATb)." Biophysical Journal 98, no. 3 (January 2010): 624a—625a. http://dx.doi.org/10.1016/j.bpj.2009.12.3418.

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Sanchez, Cesar, Luis Jaramillo-Valverde, Silvia Capristano, Gilmer Solis, Alonso Soto, Julio Valdivia-Silva, Julio A. Poterico, and Heinner Guio. "Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection." Microorganisms 11, no. 6 (May 25, 2023): 1385. http://dx.doi.org/10.3390/microorganisms11061385.

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The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.

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Kimuda, Simon G., Angela Nalwoga, Jonathan Levin, Kees L. M. C. Franken, Tom H. M. Ottenhoff, Alison M. Elliott, Stephen Cose, and Irene Andia-Biraro. "Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection." Journal of Immunology Research 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/1593143.

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Latent tuberculosis infection (LTBI) is evidence of immunological control of tuberculosis. Dormancy survival regulator (DosR) regulon-encoded proteins may have a role in the maintenance of LTBI. T cell responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were found to be most frequent among household contacts of TB cases from Uganda compared to other DosR proteins, but antibody responses were not described. We characterized antibody responses to these proteins in individuals from Uganda. Antibodies to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were measured in 68 uninfected individuals, 62 with LTBI, and 107 with active pulmonary tuberculosis (APTB) cases. There were no differences in the concentrations of antibodies to Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins between individuals with LTBI and APTB and those who were uninfected. LTBI was associated with higher concentrations of antibodies to Rv1733c in female participants [adjusted geometric mean ratio: 1.812, 95% confidence interval (CI): 1.105 2.973, and p=0.019] but not in males (p value for interaction = 0.060). Antibodies to the four DosR regulon-encoded proteins investigated may not serve as good biomarkers of LTBI in the general population. More of the M.tb proteome needs to be screened to identify proteins that induce strong antibody responses in LTBI.

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Jha, Vikas, Sathi Maiti, Dattatray Sawant, Darpan Kaur, Sankalp Kasbe, Abhishek Kumar, Badal Saiya, Shloka Shukla, Simeen Rumani, and Mrunmayi Markam. "Immunoinformatic analysis of proteins from DNA replication, repair, recombination, and restriction/modification pathway of Mycobacterium tuberculosis revealed the diagnostic potential of Rv0054 and Rv3644c." Journal of Applied Biotechnology & Bioengineering 9, no. 5 (October 27, 2022): 190–201. http://dx.doi.org/10.15406/jabb.2022.09.00309.

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Mycobacterium tuberculosis being a causative agent of tuberculosis is a powerful pathogen that has evolved to survive within the host. There are certain metabolic pathways that play a vital role in host-pathogen interaction, pathogenicity and virulence which is indicated by the pathophysiology of Mycobacterium tuberculosis (MTB). The pathways involve many proteins that are vital for MTB survival in the host. One such pathway is DNA replication, repair, recombination, and restriction/modification pathway. The study of DNA repair mechanisms in Mycobacterium tuberculosis has progressed more slowly than in other bacteria due to the technological challenges in dealing with a slow-growing pathogen. In this study, by utilizing immunoinformatic analysis & homology modelling approach, the evaluation of the proteins involved in this pathway was carried out which can lead to the discovery of potential drug targets, vaccine candidates as well as various diagnostic markers

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Yao, Yong, Neha Barghava, Johnny Kim, Michael Niederweis, and Francesca M. Marassi. "Molecular Structure and Peptidoglycan Recognition of Mycobacterium tuberculosis ArfA (Rv0899)." Journal of Molecular Biology 416, no. 2 (February 2012): 208–20. http://dx.doi.org/10.1016/j.jmb.2011.12.030.

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Papadopoulos, Andrea Olga, Christopher Ealand, Bhavna Gowan Gordhan, Michael VanNieuwenhze, and Bavesh Davandra Kana. "Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis." PLOS ONE 16, no. 11 (November 16, 2021): e0259181. http://dx.doi.org/10.1371/journal.pone.0259181.

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Mycobacterium tuberculosis, the causative agent of tuberculosis remains a global health concern, further compounded by the high rates of HIV-TB co-infection and emergence of multi- and extensive drug resistant TB, all of which have hampered efforts to eradicate this disease. As a result, novel anti-tubercular interventions are urgently required, with the peptidoglycan component of the M. tuberculosis cell wall emerging as an attractive drug target. Peptidoglycan M23 endopeptidases can function as active cell wall hydrolases or degenerate activators of hydrolases in a variety of bacteria, contributing to important processes such as bacterial growth, division and virulence. Herein, we investigate the function of the Rv0950-encoded putative M23 endopeptidase in M. tuberculosis. In silico analysis revealed that this protein is conserved in mycobacteria, with a zinc-binding catalytic site predictive of hydrolytic activity. Transcript analysis indicated that expression of Rv0950c was elevated during lag and log phases of growth and reduced in stationary phase. Deletion of Rv0950c yielded no defects in growth, colony morphology, antibiotic susceptibility or intracellular survival but caused a reduction in cell length. Staining with a monopeptide-derived fluorescent D-amino acid, which spatially reports on sites of active PG biosynthesis or repair, revealed an overall reduction in uptake of the probe in ΔRv0950c. When stained with a dipeptide probe in the presence of cell wall damaging agents, the ΔRv0950c mutant displayed reduced sidewall labelling. As bacterial peptidoglycan metabolism is important for survival and pathogenesis, the role of Rv0950c and other putative M23 endopeptidases in M. tuberculosis should be explored further.

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Teixeira, Henrique Couto, Ana Márcia Menezes Mattos, Caroline Souza Almeida, Lily Paola Martinez Abad, Kees Franken, and Tom H. M. Ottenhoff. "IgG1 and Th1 responses to DosR, Rpf and active growth phase antigens of Mycobacterium tuberculosis in Brazilian tuberculosis patients." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 65.15. http://dx.doi.org/10.4049/jimmunol.196.supp.65.15.

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Abstract Tuberculosis (TB) is serious problem worldwide. New antigens from Mycobacterium tuberculosis are being investigated in order to improve the diagnosis of latent TB infection and TB disease. In this study, serum levels of IgG1 antibodies against active growth phase antigens (ESAT-6/CFP-10, Rv0717 and Rv3353), dormancy-related (DosR) antigens (Rv1733, Rv1737, Rv2029 and Rv2628), and resuscitation promoting factors (Rpfs Rv0867 and Rv2389) were evaluated in patients with TB before and after chemotherapy using ELISA. Antigen-induced IFN-γ, TNF-α, IL-17, IL-10 and IL-4 were evaluated in supernatants of PBMC cultures. Our results indicate that patients with pulmonary TB express high levels of IgG1 antibodies against ESAT-6/CFP-10, Rv0717, Rv3353, Rv1733, Rv2029 and Rv2628 Rv0867 in the active phase of the disease in comparison to healthy controls (p<0.001). These levels declined to control levels after the completion of six months treatment. ROC analysis confirmed the good performance of Rv0717, Rv1733, Rv3353, Rv0867, Rv2029 and Rv2628 antigens. Interestingly, Rv0717 and Rv1733 antigens induced an IgG1 peak response after 1–3 months of chemotherapy (P<0.01). Similarly, IFN-γ and TNF-α peaked early during treatment in response to ESAT-6/CFP-10, Rv1733 and Rv2029, and declined to control levels after 6 months of chemotherapy. The study groups did not differ in respect to IL-17, IL-10 and IL-4. Taken together, these data further reinforce a possible correlation of IgG1 production with Th1 responses in TB. Moreover, detecting IgG1 antibodies against M. tuberculosis antigens, including DosR and Rpf proteins, may represent an additional tool in the diagnosis of tuberculosis. Financial support: FAPEMIG, CNPq and CAPES, EU and NWO-TOP.

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Fang, Haihong, Dan Yu, Yuzhi Hong, Xiaodan Zhou, Chuanyou Li, and Baolin Sun. "The LuxR family regulator Rv0195 modulates Mycobacterium tuberculosis dormancy and virulence." Tuberculosis 93, no. 4 (July 2013): 425–31. http://dx.doi.org/10.1016/j.tube.2013.04.005.

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Gurvitz, Aner, J. Kalervo Hiltunen, and Alexander J. Kastaniotis. "Heterologous Expression of Mycobacterial Proteins in Saccharomyces cerevisiae Reveals Two Physiologically Functional 3-Hydroxyacyl-Thioester Dehydratases, HtdX and HtdY, in Addition to HadABC and HtdZ." Journal of Bacteriology 191, no. 8 (January 9, 2009): 2683–90. http://dx.doi.org/10.1128/jb.01046-08.

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ABSTRACT We report on Mycobacterium tuberculosis Rv0241c and Rv3389c, representing two physiologically functional 3-hydroxyacyl-thioester dehydratases (Htd). These enzymes are potentially entrained in type 2 fatty acid synthase (FASII). Mycobacterial FASII is involved in the synthesis of mycolic acids, which are the major constituents of the protective layer around the pathogen, shielding it from noxious chemicals and the host's immune system. Mycolic acids are additionally associated with the virulence and resilience of M. tuberculosis. Here, Rv0241c and Rv3389c, which are distinct from the previously identified heterodimers Rv0635-Rv0636 (HadAB) and Rv0636-Rv0637 (HadBC) but also the homodimer Rv0130 (HtdZ), were identified by expressing the corresponding candidate open reading frames in Saccharomyces cerevisiae htd2Δ cells lacking mitochondrial 3-hydroxyacyl-acyl carrier protein dehydratase activity, followed by scoring for phenotype rescue. The htd2Δ mutant fails to produce sufficient levels of lipoic acid and does not respire or grow on nonfermentable carbon sources. Soluble protein extracts made from mutant htd2Δ cells expressing mitochondrially targeted Rv0241c or Rv3389c contained 3-hydroxyacyl-thioester hydratase activity. Moreover, mutant yeast cells expressing Rv0241c or Rv3389c were able to recover their respiratory growth on glycerol medium and efficiently reduce 2,3,5-triphenyltetrazolium chloride. Additionally, expression of mitochondrial Rv0241c or Rv3389c in htd2Δ cells also restored de novo lipoic acid synthesis to 92 and 40% of the level in the wild-type strain, respectively. We propose naming Rv0241c and Rv3389c as HtdX and HtdY, respectively, and discuss the implications of our finding with reference to Rv0098, a candidate mycobacterial FabZ homologue with intrinsic thioesterase and hydratase activities that lacks the eukaryotic-like hydratase-2 motif.

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Cáceres, Silvia Marcela, Marisol Ocampo, Gabriela Arévalo-Pinzón, Ronald Andrés Jimenez, Manuel Elkin Patarroyo, and Manuel Alfonso Patarroyo. "The Mycobacterium tuberculosis membrane protein Rv0180c: Evaluation of peptide sequences implicated in mycobacterial invasion of two human cell lines." Peptides 32, no. 1 (January 2011): 1–10. http://dx.doi.org/10.1016/j.peptides.2010.09.017.

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Junqueira-Kipnis, Ana Paula, Carine de Castro Souza, Ana Carolina de Oliveira Carvalho, Fabio Muniz de Oliveira, Vinnycius Pereira Almeida, Alisson Rodrigues de Paula, Mara Rubia Celes, and André Kipnis. "Protease-Based Subunit Vaccine in Mice Boosts BCG Protection against Mycobacterium tuberculosis." Vaccines 10, no. 2 (February 16, 2022): 306. http://dx.doi.org/10.3390/vaccines10020306.

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The significant number of people with latent and active tuberculosis infection requires further efforts to develop new vaccines or improve the Bacillus Calmette-Guérin (BCG), which is the only approved vaccine against this disease. In this study, we developed a recombinant fusion protein (PEPf) containing high-density immunodominant epitope sequences from Rv0125, Rv2467, and Rv2672 Mycobacterium tuberculosis (Mtb) proteases that proved immunogenic and used it to develop a recombinant BCG vaccine expressing the fusion protein. After challenging using Mtb, a specific immune response was recalled, resulting in a reduced lung bacterial load with similar protective capabilities to BCG. Thus BCG PEPf failed to increase the protection conferred by BCG. The PEPf was combined with Advax4 adjuvant and tested as a subunit vaccine using a prime-boost strategy. PEPf + Advax4 significantly improved protection after Mtb challenge, with a reduction in bacterial load in the lungs. Our results confirm that Mtb proteases can be used to develop vaccines against tuberculosis and that the use of the recombinant PEPf subunit protein following a prime-boost regimen is a promising strategy to improve BCG immunity.

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Rupa, L., A. Srikantam, SS Lakshmana Rao, U. Devi, and KSR Sivasai. "Molecular analysis of Rv0679c and Rv0180c genes of Mycobacterium tuberculosis from clinical isolates of pulmonary tuberculosis." Indian Journal of Medical Microbiology 34, no. 4 (October 2016): 471–75. http://dx.doi.org/10.4103/0255-0857.195357.

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Yao, Yong, Neha Barghava, Michael Niederwiser, and Francesca Marassi. "Solution Structure and Peptidoglycan Interaction of Rv0899, a Virulence Factor from Mycobacterium Tuberculosis." Biophysical Journal 102, no. 3 (January 2012): 422a. http://dx.doi.org/10.1016/j.bpj.2011.11.2310.

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Bondoc, Jasper Marc G., Hiten J. Gutka, Mashal M. Almutairi, Ryan Patwell, Maxwell W. Rutter, Nina M. Wolf, Ram Samudrala, et al. "Rv0100, a proposed acyl carrier protein in Mycobacterium tuberculosis: expression, purification and crystallization. Corrigendum." Acta Crystallographica Section F Structural Biology Communications 76, no. 4 (April 1, 2020): 192–93. http://dx.doi.org/10.1107/s2053230x2000271x.

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Sun, Y., Y. Wang, H. Wang, S. Wang, G. Ping, and L. Zhang. "HLA-A*0201-restricted CTL epitopes in Rv0350 and Rv0351 of latent Mycobacterium tuberculosis." International Journal of Infectious Diseases 21 (April 2014): 306. http://dx.doi.org/10.1016/j.ijid.2014.03.1054.

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Tripathi, Sarita, Rahul Yadav, Anupam Jain, Surya V. S. R. K. Pulavarti, Prem Prakash Pathak, Ajaya Kumar Behera, and Ashish Arora. "Resonance assignments and secondary structure prediction of secretory protein Rv0603 from Mycobacterium tuberculosis H37Rv." Biomolecular NMR Assignments 14, no. 2 (May 20, 2020): 217–19. http://dx.doi.org/10.1007/s12104-020-09948-5.

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Marassi, Francesca M. "Mycobacterium tuberculosis Rv0899 defines a family of membrane proteins widespread in nitrogen-fixing bacteria." Proteins: Structure, Function, and Bioinformatics 79, no. 10 (August 26, 2011): 2946–55. http://dx.doi.org/10.1002/prot.23151.

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Black, Gillian F., Bonnie A. Thiel, Martin O. Ota, Shreemanta K. Parida, Richard Adegbola, W. Henry Boom, Hazel M. Dockrell, et al. "Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa." Clinical and Vaccine Immunology 16, no. 8 (August 2009): 1203–12. http://dx.doi.org/10.1128/cvi.00111-09.

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ABSTRACT Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in >75% of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity.

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Bashiri, Ghader, Christopher J. Squire, Edward N. Baker, and Nicole J. Moreland. "Expression, purification and crystallization of native and selenomethionine labeled Mycobacterium tuberculosis FGD1 (Rv0407) using a Mycobacterium smegmatis expression system." Protein Expression and Purification 54, no. 1 (July 2007): 38–44. http://dx.doi.org/10.1016/j.pep.2007.01.014.

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Schiller, Irene, H. Martin Vordermeier, W. Ray Waters, Mitchell Palmer, Tyler Thacker, Adam Whelan, Roland Hardegger, Beatrice Marg-Haufe, Alex Raeber, and Bruno Oesch. "Assessment of Mycobacterium tuberculosis OmpATb as a Novel Antigen for the Diagnosis of Bovine Tuberculosis." Clinical and Vaccine Immunology 16, no. 9 (July 8, 2009): 1314–21. http://dx.doi.org/10.1128/cvi.00151-09.

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ABSTRACT In the search for better tools to control bovine tuberculosis, the development of diagnostic tests with improved specificity and sensitivity has a high priority. We chose to search for novel immunodiagnostic reagents. In this study, Rv0899 (outer membrane protein A of Mycobacterium tuberculosis [OmpATb]) was evaluated as a stimulation antigen in a gamma interferon (IFN-γ) release assay to diagnose bovine tuberculosis. OmpATb induced IFN-γ responses in cattle experimentally infected with M. bovis as early and as persistently as ESAT-6 and CFP-10, the current lead diagnostic antigens. In naturally infected cattle, OmpATb stimulated IFN-γ production in 22 of 26 animals (85%). Importantly, OmpATb detected a portion of M. bovis-infected cattle which did not respond to ESAT-6 and CFP-10 (five of six cattle). The combined diagnostic sensitivity of OmpATb, ESAT-6, and CFP-10 for a preselected group consisting of naturally infected cattle with an overrepresentation of ESAT-6/CFP-10 nonresponders was 96% (25 of 26 animals). The specificity of OmpATb for uninfected cattle was 100% (27 cattle were tested; 12 of them gave false-positive results with tuberculins). In summary, our results indicate that OmpATb has the potential to enhance the sensitivity of previously described diagnostic tests based on ESAT-6 and CFP-10 and that the combined use of OmpATb, ESAT-6, CFP-10, and other proteins may achieve at least equal sensitivity to that obtained with purified protein derivative, but at a higher specificity. Further studies evaluating the diagnostic performance of OmpATb in combination with other proteins are ongoing.

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Feuerriegel, Silke, Claudio U. Köser, Davide Baù, Sabine Rüsch-Gerdes, David K. Summers, John A. C. Archer, Marc A. Marti-Renom, and Stefan Niemann. "Impact offgd1andddnDiversity in Mycobacterium tuberculosis Complex onIn VitroSusceptibility to PA-824." Antimicrobial Agents and Chemotherapy 55, no. 12 (September 19, 2011): 5718–22. http://dx.doi.org/10.1128/aac.05500-11.

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ABSTRACTPA-824 is a promising drug candidate for the treatment of tuberculosis (TB). It is in phase II clinical trials as part of the first newly designed regimen containing multiple novel antituberculosis drugs (PA-824 in combination with moxifloxacin and pyrazinamide). However, given that the genes involved in resistance against PA-824 are not fully conserved in theMycobacterium tuberculosiscomplex (MTBC), this regimen might not be equally effective against different MTBC genotypes. To investigate this question, we sequenced two PA-824 resistance genes (fgd1[Rv0407] andddn[Rv3547]) in 65 MTBC strains representing major phylogenetic lineages. The MICs of representative strains were determined using the modified proportion method in the Bactec MGIT 960 system. Our analysis revealed single-nucleotide polymorphisms in both genes that were specific either for several genotypes or for individual strains, yet none of these mutations significantly affected the PA-824 MICs (≤0.25 μg/ml). These results were supported byin silicomodeling of the mutations identified in Fgd1. In contrast, “Mycobacterium canettii” strains displayed a higher MIC of 8 μg/ml. In conclusion, we found a large genetic diversity in PA-824 resistance genes that did not lead to elevated PA-824 MICs. In contrast,M. canettiistrains had MICs that were above the plasma concentrations of PA-824 documented so far in clinical trials. AsM. canettiiis also intrinsically resistant against pyrazinamide, new regimens containing PA-824 and pyrazinamide might not be effective in treatingM. canettiiinfections. This finding has implications for the design of multiple ongoing clinical trials.

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Kirksey, Meghan A., Anna D. Tischler, Roxane Siméone, Katherine B. Hisert, Swapna Uplekar, Christophe Guilhot, and John D. McKinney. "Spontaneous Phthiocerol Dimycocerosate-Deficient Variants of Mycobacterium tuberculosis Are Susceptible to Gamma Interferon-Mediated Immunity." Infection and Immunity 79, no. 7 (May 16, 2011): 2829–38. http://dx.doi.org/10.1128/iai.00097-11.

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ABSTRACTOnset of the adaptive immune response in mice infected withMycobacterium tuberculosisis accompanied by slowing of bacterial replication and establishment of a chronic infection. Stabilization of bacterial numbers during the chronic phase of infection is dependent on the activity of the gamma interferon (IFN-γ)-inducible nitric oxide synthase (NOS2). Previously, we described a differential signature-tagged mutagenesis screen designed to identifyM. tuberculosis“counterimmune” mechanisms and reported the isolation of three mutants in the H37Rv strain background containing transposon insertions in therv0072,rv0405, andrv2958cgenes. These mutants were impaired for replication and virulence in NOS2−/−mice but were growth-proficient and virulent in IFN-γ−/−mice, suggesting that the disrupted genes were required for bacterial resistance to an IFN-γ-dependent immune mechanism other than NOS2. Here, we report that the attenuation of these strains is attributable to an underlying transposon-independent deficiency in biosynthesis of phthiocerol dimycocerosate (PDIM), a cell wall lipid that is required for full virulence in mice. We performed whole-genome resequencing of a PDIM-deficient clone and identified a spontaneous point mutation in the putative polyketide synthase PpsD that results in a G44C amino acid substitution. We demonstrate by complementation with the wild-typeppsDgene and reversion of theppsDgene to the wild-type sequence that theppsD(G44C) point mutation is responsible for PDIM deficiency, virulence attenuation in NOS2−/−and wild-type C57BL/6 mice, and a growth advantagein vitroin liquid culture. We conclude that PDIM biosynthesis is required forM. tuberculosisresistance to an IFN-γ-mediated immune response that is independent of NOS2.

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Grant, Nicole L., Alexis J. Balgeman, Amy L. Ellis, Shelby L. O'Connor, Charles A. Scanga, and JoAnne L. Flynn. "Epitope mapping of Mycobacterium tuberculosis proteins using a non-human primate model of infection." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 177.29. http://dx.doi.org/10.4049/jimmunol.202.supp.177.29.

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Abstract Mycobacterium tuberculosis, the causative agent of tuberculosis, is the leading cause of death by a single infectious agent worldwide. Many studies have focused on the necessity of T cells in combating tuberculosis, particularly at the primary site of infection in the lungs, the granuloma. In spite of their importance in TB disease, very low frequencies of T cells in the granuloma produce cytokine. Our objective is to determine the number and function of Mtb specific T cells in tissues and the periphery using tetramers. We have developed non-human primate (NHP) models of Mtb infection which recapitulate human infection, however, both humans and many NHPs have high MHC variability making studies aimed at understanding the role of specific T cells at the site of infection difficult. For this study, we used a Mauritian cynomolgus macaque (MCM) model, due to their limited MHC variability, to map epitopes of Mtb proteins Rv1196 and Rv0125. Using homozygous animals we found that both proteins elicit peak peripheral IFNγ responses early post infection. We mapped epitopes using pooled or individual peptides in IFNγ Elispots and determined the peak binding regions. We tested allele restriction using RM3 cells expressing major M1 alleles. These data can be used to design tetramers which are vital in determining the number and functionality of antigen specific T cells in the periphery, LN, and lung granulomas of infected MCMs. Understanding the number and function of these Mtb specific T cells following infection will provide a deeper understanding of the role T cells play in pathology and bacterial containment.

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Sun, Xian, Lu Zhang, Jun Jiang, Mark Ng, Zhenling Cui, Juntao Mai, Sang Kyun Ahn, et al. "Transcription factors Rv0081 and Rv3334 connect the early and the enduring hypoxic response of Mycobacterium tuberculosis." Virulence 9, no. 1 (September 26, 2018): 1468–82. http://dx.doi.org/10.1080/21505594.2018.1514237.

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Byun, Eui-Hong, Woo Sik Kim, A.-Rum Shin, Jong-Seok Kim, Jake Whang, Choul-Jae Won, Yohan Choi, et al. "Rv0315, a novel immunostimulatory antigen of Mycobacterium tuberculosis, activates dendritic cells and drives Th1 immune responses." Journal of Molecular Medicine 90, no. 3 (October 13, 2011): 285–98. http://dx.doi.org/10.1007/s00109-011-0819-2.

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Li, Juan, Chaowei Shi, Yuan Gao, Kaiqi Wu, Pan Shi, Chaohua Lai, Liu Chen, Fangming Wu, and Changlin Tian. "Structural Studies of Mycobacterium tuberculosis Rv0899 Reveal a Monomeric Membrane-Anchoring Protein with Two Separate Domains." Journal of Molecular Biology 415, no. 2 (January 2012): 382–92. http://dx.doi.org/10.1016/j.jmb.2011.11.016.

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Kashyap, Rajpal S., Sonali M. Saha, Khushboo J. Nagdev, Sanjeevani S. Kelkar, Hemant J. Purohit, Girdhar M. Taori, and Hatim F. Daginawala. "Diagnostic Markers for Tuberculosis Ascites: A Preliminary Study." Biomarker Insights 5 (January 2010): BMI.S5196. http://dx.doi.org/10.4137/bmi.s5196.

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Objective The diagnosis of tuberculosis (TB) ascites is problematic. Delay in the diagnosis and treatment of TB ascites are considered to be major factors that contribute to the high mortality of TB. This study identifies specific protein markers in ascitic fluid which will be useful in diagnosis of TB ascites. Methods We used Two-Dimensional Electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry, immunoblot analysis and Enzyme Linked Immunosorbent assay (ELISA) as a comprehensive quantitative proteomic screening system for the diagnosis of TB ascites. Results The screen identified several antigens of interest: a 30-kilodalton (kDa) protein that demonstrated significant homology to the antigen 85B and 85C (Ag 85) complex; a 65-kDa protein that corresponded to Mycobacterium tuberculosis (MTB) heat shock protein 65 (65-kDa HSP), Rv0440; a 14-kDa protein and 71-kDa protein that exhibits an amino acid sequence identical to that of MTB heat shock protein 14 (14-kDa HSP), GroES; and MTB heat shock protein 71 (71-kDa HSP), Rv0350 respectively. ELISA confirmed that TB ascites patients were consistently positive for these antigens at higher rates than non-TB ascites patients. Conclusion The 65-kDa HSP, 71-kDa HSP, 14-kDa HSP and Ag 85 complex proteins may serve as very useful diagnostic markers for TB ascites.

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Kassa, Desta, Leonie Ran, Wudneh Geberemeskel, Mekashaw Tebeje, Amelewerk Alemu, Alemayehu Selase, Belete Tegbaru, et al. "Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis." Clinical and Vaccine Immunology 19, no. 12 (September 26, 2012): 1907–15. http://dx.doi.org/10.1128/cvi.00482-12.

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ABSTRACTCharacterizing host immune responses to molecular targets ofMycobacterium tuberculosisis essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series ofM. tuberculosisantigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n= 34) was stimulatedin vitrowithM. tuberculosisantigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classicalM. tuberculosisantigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to severalM. tuberculosisantigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenicM. tuberculosisantigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets ofM. tuberculosisantigens may be promising for the development of immunodiagnostics.

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Hahn, Mi-Young, Sahadevan Raman, Mauricio Anaya, and Robert N. Husson. "The Mycobacterium tuberculosis Extracytoplasmic-Function Sigma Factor SigL Regulates Polyketide Synthases and Secreted or Membrane Proteins and Is Required for Virulence." Journal of Bacteriology 187, no. 20 (October 15, 2005): 7062–71. http://dx.doi.org/10.1128/jb.187.20.7062-7071.2005.

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ABSTRACT Mycobacterium tuberculosis sigL encodes an extracytoplasmic function (ECF) sigma factor and is adjacent to a gene for a membrane protein (Rv0736) that contains a conserved HXXXCXXC sequence. This motif is found in anti-sigma factors that regulate several ECF sigma factors, including those that control oxidative stress responses. In this work, SigL and Rv0736 were found to be cotranscribed, and the intracellular domain of Rv0736 was shown to interact specifically with SigL, suggesting that Rv0736 may encode an anti-sigma factor of SigL. An M. tuberculosis sigL mutant was not more susceptible than the parental strain to several oxidative and nitrosative stresses, and sigL expression was not increased in response to these stresses. In vivo, sigL is expressed from a weak SigL-independent promoter and also from a second SigL-dependent promoter. To identify SigL-regulated genes, sigL was overexpressed and microarray analysis of global transcription was performed. Four small operons, sigL (Rv0735)-Rv0736, mpt53 (Rv2878c)-Rv2877c, pks10 (Rv1660)-pks7 (Rv1661), and Rv1139c-Rv1138c, were among the most highly upregulated genes in the sigL-overexpressing strain. SigL-dependent transcription start sites of these operons were mapped, and the consensus promoter sequences TGAACC in the −35 region and CGTgtc in the −10 region were identified. In vitro, purified SigL specifically initiated transcription from the promoters of sigL, mpt53, and pks10. Additional genes, including four PE_PGRS genes, appear to be regulated indirectly by SigL. In an in vivo murine infection model, the sigL mutant strain showed marked attenuation, indicating that the sigL regulon is important in M. tuberculosis pathogenesis.

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Tiwari, Bhavana Mishra, Nisha Kannan, Lakshmi Vemu, and Tirumalai R. Raghunand. "The Mycobacterium tuberculosis PE Proteins Rv0285 and Rv1386 Modulate Innate Immunity and Mediate Bacillary Survival in Macrophages." PLoS ONE 7, no. 12 (December 17, 2012): e51686. http://dx.doi.org/10.1371/journal.pone.0051686.

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Lee, J. J., H. Y. Kang, W.-I. Lee, S. Y. Cho, Y. J. Kim, and H. J. Lee. "Efflux pump gene expression study using RNA-seq in multidrug-resistant TB." International Journal of Tuberculosis and Lung Disease 25, no. 12 (December 1, 2021): 974–81. http://dx.doi.org/10.5588/ijtld.21.0117.

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BACKGROUND: The mechanism underlying kanamycin (KM) resistance in Mycobacterium tuberculosis is not well understood, although efflux pump proteins are thought to play a role. This study used RNA-seq data to investigate changes in the expression levels of efflux pump genes following exposure to KM.METHODS: RNA expression of efflux pump and regulatory genes following exposure to different concentrations of KM (minimum inhibitory concentration MIC 25 and MIC50) in rrs wild-type strain and rrs A1401G mutated strain were compared with the control group.RESULTS: The selected strains had differential RNA expression patterns. Among the 71 putative efflux pump and regulatory genes, 46 had significant fold changes, and 12 genes (Rv0842, Rv1146, Rv1258c, Rv1473, Rv1686c, Rv1687c, Rv1877, Rv2038c, Rv3065, Rv3197a, Rv3728 and Rv3789) that were overexpressed following exposure to KM were thought to contribute to drug resistance. Rv3197A (whiB7) showed a distinct fold change based on the concentration of KM.CONCLUSION: The significant changes in the expression of the efflux pump and regulatory genes following exposure to KM may provide insights into the identification of a new resistance mechanism.

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47

Singh, Khundrakpam Herojit, Savita Yadav, Deepak Kumar, and Bichitra Kumar Biswal. "The crystal structure of an essential high-temperature requirement protein HtrA1 (Rv1223) from Mycobacterium tuberculosis reveals its unique features." Acta Crystallographica Section D Structural Biology 74, no. 9 (September 1, 2018): 906–21. http://dx.doi.org/10.1107/s205979831800952x.

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High-temperature requirement A (HtrA) proteins, which are members of the heat-shock-induced serine protease family, are involved in extracytoplasmic protein quality control and bacterial survival strategies under stress conditions, and are associated with the virulence of several pathogens; they are therefore major drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1 (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a transmembrane helix and a periplasmic region. Here, the crystal structure of the periplasmic region consisting of a protease domain (PD) and a PDZ domain from an M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 Å resolution. Although the mHtrA1S387A PD shows structural features similar to those of other HtrAs, its loops, particularly L3 and LA, display different conformations. Loop L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a transition from an active to an inactive conformation, as reported for an equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer formation owing to its length (50 amino acids) in DegP, is very short in mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and therefore lacks essential interactions for the formation of higher oligomers. Notably, a well ordered loop known as the insertion clamp in the PDZ domain interacts with the protease domain of the adjacent molecule, which possibly aids in the stabilization of a trimeric functional unit of this enzyme. The three-dimensional structure of mHtrA1S387A presented here will be useful in the design of enzyme-specific antituberculosis inhibitors.

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48

Zhang, Le, Qi Zhong, Lang Bao, Ying Zhang, Lei Gao, Bi Huang, and Hui-Dong Zhang. "Rv0901 from <i>Mycobacterium tuberculosis</i>, a Possible Novel Virulent Gene Proved through the Recombinant <i>Mycobacterium smegmatis</i>." Japanese Journal of Infectious Diseases 62, no. 1 (January 28, 2009): 26–31. http://dx.doi.org/10.7883/yoken.jjid.2009.26.

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Sundar, Shobana, Lokesh Thangamani, Gowdham Manivel, Praveen Kumar, and Shanmughavel Piramanayagam. "Rv0807, a putative phospholipase A2 of Mycobacterium tuberculosis; Elucidation through sequence analysis, homology modeling, molecular docking and molecular dynamics studies of potential substrates and inhibitors." Journal of Biomolecular Structure and Dynamics 38, no. 13 (October 24, 2019): 3990–4004. http://dx.doi.org/10.1080/07391102.2019.1677499.

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50

Kalyani, B. Sudha, Radhika Kunamneni, Megha Wal, Amitabh Ranjan, and Ranjan Sen. "A NusG paralogue from Mycobacterium tuberculosis, Rv0639, has evolved to interact with ribosomal protein S10 (Rv0700) but not to function as a transcription elongation–termination factor." Microbiology 161, no. 1 (January 1, 2015): 67–83. http://dx.doi.org/10.1099/mic.0.083709-0.

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Journal articles on the topic 'Rv0805 - Mycobacterium Tuberculosis'

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