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Journal articles on the topic 'Mycobacterium tuberculosis σ Factors'

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Author: Grafiati

Published: 6 September 2023

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1

Rodrigue, Sébastien, Joëlle Brodeur, Pierre-Étienne Jacques, Alain L. Gervais, Ryszard Brzezinski, and Luc Gaudreau. "Identification of Mycobacterial σ Factor Binding Sites by Chromatin Immunoprecipitation Assays." Journal of Bacteriology 189, no. 5 (December 8, 2006): 1505–13. http://dx.doi.org/10.1128/jb.01371-06.

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ABSTRACT Mycobacterium tuberculosis and Mycobacterium bovis are responsible for infections that cause a substantial amount of death, suffering, and loss around the world. Still, relatively little is known about the mechanisms of gene expression in these bacteria. Here, we used genome-wide location assays to identify direct target genes for mycobacterial σ factors. Chromatin immunoprecipitation assays were performed with M. bovis BCG for Myc-tagged proteins expressed using an anhydrotetracycline-inducible promoter, and enriched DNA fragments were hybridized to a microarray representing intergenic regions from the M. tuberculosis H37Rv genome. Several putative target genes were validated by quantitative PCR. The corresponding transcriptional start sites were identified for σF, σC, and σK, and consensus promoter sequences are proposed. Our conclusions were supported by the results of in vitro transcription assays. We also examined the role of each holoenzyme in the expression of σ factor genes. Our results revealed that many σ factors are expressed from autoregulated promoters.

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2

Manganelli, Riccardo, Roberta Proveddi, Sebastien Rodrigue, Jocelyn Beaucher, Luc Gaudreau, and Issar Smith. "σ Factors and Global Gene Regulation in Mycobacterium tuberculosis." Journal of Bacteriology 186, no. 4 (February 15, 2004): 895–902. http://dx.doi.org/10.1128/jb.186.4.895-902.2004.

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3

Manganelli, Riccardo, Roberta Provvedi, Sebastien Rodrigue, Jocelyn Beaucher, Luc Gaudreau, and Issar Smith. "σ Factors and Global Gene Regulation in Mycobacterium tuberculosis." Journal of Bacteriology 186, no. 8 (April 15, 2004): 2516. http://dx.doi.org/10.1128/jb.186.8.2516.2004.

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4

Mallick Gupta, A., S. Mukherjee, A. Dutta, J. Mukhopadhyay, D. Bhattacharyya, and S. Mandal. "Identification of a suitable promoter for the sigma factor of Mycobacterium tuberculosis." Mol. BioSyst. 13, no. 11 (2017): 2370–78. http://dx.doi.org/10.1039/c7mb00317j.

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Promoter binding specificity is one of the important characteristics of transcription by Mycobacterium tuberculosis (Mtb) sigma (σ) factors, which remains unexplored due to limited structural evidence.

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5

Thakur, Krishan Gopal, Anagha Madhusudan Joshi, and B. Gopal. "Structural and Biophysical Studies on Two Promoter Recognition Domains of the Extra-cytoplasmic Function σ Factor σC from Mycobacterium tuberculosis." Journal of Biological Chemistry 282, no. 7 (December 4, 2006): 4711–18. http://dx.doi.org/10.1074/jbc.m606283200.

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σ factors are transcriptional regulatory proteins that bind to the RNA polymerase and dictate gene expression. The extracytoplasmic function (ECF) σ factors govern the environment dependent regulation of transcription. ECF σ factors have two domains σ2 and σ4 that recognize the -10 and -35 promoter elements. However, unlike the primary σ factor σA, the ECF σ factors lack σ3, a region that helps in the recognition of the extended -10 element and σ1.1, a domain involved in the autoinhibition of σA in the absence of core RNA polymerase. Mycobacterium tuberculosis σC is an ECF σ factor that is essential for the pathogenesis and virulence of M. tuberculosis in the mouse and guinea pig models of infection. However, unlike other ECF σ factors, σC does not appear to have a regulatory anti-σ factor located in the same operon. We also note that M. tuberculosis σC differs from the canonical ECF σ factors as it has an N-terminal domain comprising of 126 amino acids that precedes the σC2 and σC4 domains. In an effort to understand the regulatory mechanism of this protein, the crystal structures of the σC2 and σC4 domains of σC were determined. These promoter recognition domains are structurally similar to the corresponding domains of σA despite the low sequence similarity. Fluorescence experiments using the intrinsic tryptophan residues of σC2 as well as surface plasmon resonance measurements reveal that the σC2 and σC4 domains interact with each other. Mutational analysis suggests that the Pribnow box-binding region of σC2 is involved in this interdomain interaction. Interaction between the promoter recognition domains in M. tuberculosis σC are thus likely to regulate the activity of this protein even in the absence of an anti-σ factor.

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6

Goutam, Kapil, Arvind Kumar Gupta, and Balasubramanian Gopal. "Crystallographic studies of the extracytoplasmic function σ factor σJfromMycobacterium tuberculosis." Acta Crystallographica Section F Structural Biology Communications 71, no. 8 (July 28, 2015): 946–50. http://dx.doi.org/10.1107/s2053230x15009577.

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Mycobacterium tuberculosishas multiple σ factors which enable the bacterium to reprogram its transcriptional machinery under diverse environmental conditions. σJ, an extracytoplasmic function σ factor, is upregulated in late stationary phase cultures and during human macrophage infection. σJgoverns the cellular response to hydrogen peroxide-mediated oxidative stress. σJdiffers from other canonical σ factors owing to the presence of a SnoaL_2 domain at the C-terminus. σJcrystals belonged to the tetragonal space groupI422, with unit-cell parametersa=b= 133.85,c= 75.08 Å. Diffraction data were collected to 2.16 Å resolution on the BM14 beamline at the European Synchrotron Radiation Facility (ESRF).

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7

Fontán, P. A., M. I. Voskuil, M. Gomez, D. Tan, M. Pardini, R. Manganelli, L. Fattorini, G. K. Schoolnik, and I. Smith. "The Mycobacterium tuberculosis Sigma Factor σB Is Required for Full Response to Cell Envelope Stress and Hypoxia In Vitro, but It Is Dispensable for In Vivo Growth." Journal of Bacteriology 191, no. 18 (July 10, 2009): 5628–33. http://dx.doi.org/10.1128/jb.00510-09.

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ABSTRACT The numerous sigma (σ) factors present in Mycobacterium tuberculosis are indicative of the adaptability of this pathogen to different environmental conditions. In this report, we describe the M. tuberculosis σB regulon and the phenotypes of an M. tuberculosis sigB mutant strain exposed to cell envelope stress, oxidative stress, and hypoxia. The sigB mutant was especially defective in survival under hypoxic conditions in vitro, but it was not attenuated for growth in THP-1 cells or during mouse and guinea pig infection.

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8

Vishwanath, Sneha, Sunaina Banerjee, Anil K. Jamithireddy, Narayanaswamy Srinivasan, Balasubramanian Gopal, and Jayanta Chatterjee. "Design, Synthesis, and Experimental Validation of Peptide Ligands Targeting Mycobacterium tuberculosis σ Factors." Biochemistry 56, no. 16 (April 12, 2017): 2209–18. http://dx.doi.org/10.1021/acs.biochem.6b01267.

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9

Fang, Chengli, Lingting Li, Liqiang Shen, Jing Shi, Sheng Wang, Yu Feng, and Yu Zhang. "Structures and mechanism of transcription initiation by bacterial ECF factors." Nucleic Acids Research 47, no. 13 (May 27, 2019): 7094–104. http://dx.doi.org/10.1093/nar/gkz470.

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Abstract Bacterial RNA polymerase (RNAP) forms distinct holoenzymes with extra-cytoplasmic function (ECF) σ factors to initiate specific gene expression programs. In this study, we report a cryo-EM structure at 4.0 Å of Escherichia coli transcription initiation complex comprising σE—the most-studied bacterial ECF σ factor (Ec σE-RPo), and a crystal structure at 3.1 Å of Mycobacterium tuberculosis transcription initiation complex with a chimeric σH/E (Mtb σH/E-RPo). The structure of Ec σE-RPo reveals key interactions essential for assembly of E. coli σE-RNAP holoenzyme and for promoter recognition and unwinding by E. coli σE. Moreover, both structures show that the non-conserved linkers (σ2/σ4 linker) of the two ECF σ factors are inserted into the active-center cleft and exit through the RNA-exit channel. We performed secondary-structure prediction of 27,670 ECF σ factors and find that their non-conserved linkers probably reach into and exit from RNAP active-center cleft in a similar manner. Further biochemical results suggest that such σ2/σ4 linker plays an important role in RPo formation, abortive production and promoter escape during ECF σ factors-mediated transcription initiation.

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10

Jamithireddy, Anil Kumar, Ashish Runthala, and Balasubramanian Gopal. "Evaluation of specificity determinants in Mycobacterium tuberculosis σ/anti-σ factor interactions." Biochemical and Biophysical Research Communications 521, no. 4 (January 2020): 900–906. http://dx.doi.org/10.1016/j.bbrc.2019.10.198.

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11

Rodrigue, Sébastien, Roberta Provvedi, Pierre-Étienne Jacques, Luc Gaudreau, and Riccardo Manganelli. "The σ factors ofMycobacterium tuberculosis." FEMS Microbiology Reviews 30, no. 6 (November 2006): 926–41. http://dx.doi.org/10.1111/j.1574-6976.2006.00040.x.

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12

Banerjee, Rajdeep, Paulami Rudra, Abinit Saha, and Jayanta Mukhopadhyay. "Recombinant Reporter Assay Using Transcriptional Machinery of Mycobacterium tuberculosis." Journal of Bacteriology 197, no. 3 (December 1, 2014): 646–53. http://dx.doi.org/10.1128/jb.02445-14.

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Development of anin vivogene reporter assay to assess interactions among the components of the transcription machinery inMycobacterium tuberculosisremains a challenge to scientists due to the tediousness of generation of mutant strains of the extremely slow-growing bacterium. We have developed a recombinant mCherry reporter assay that enables us to monitor the interactions ofMycobacterium tuberculosistranscriptional regulators with its promotersin vivoinEscherichia coli. The assay involves a three-plasmid expression system inE. coliwherein two plasmids are responsible forM. tuberculosisRNA polymerase (RNAP) production and the third plasmid harbors the mCherry reporter gene expression cassette under the control of either a σ factor or a transcriptional regulator-dependent promoter. We observed that the endogenousE. coliRNAP and σ factor do not interfere with the assay. By using the reporter assay, we found that the functional interaction ofM. tuberculosiscyclic AMP receptor protein (CRP) occurs with its own RNA polymerase, not with theE. colipolymerase. Performing the recombinant reporter assay inE. coliis much faster than if performed inM. tuberculosisand avoids the hazard of handling the pathogenic bacterium. The approach could be expanded to develop reporter assays for other pathogenic and slow-growing bacterial systems.

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13

Gomez, J. E., J.-M. Chen, and W. R. Bishai. "Sigma factors of Mycobacterium tuberculosis." Tubercle and Lung Disease 78, no. 3-4 (January 1997): 175–83. http://dx.doi.org/10.1016/s0962-8479(97)90024-1.

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14

Sundararajan, Sadhana, and Rajiniraja Muniyan. "Latent tuberculosis: interaction of virulence factors in Mycobacterium tuberculosis." Molecular Biology Reports 48, no. 8 (August 2021): 6181–96. http://dx.doi.org/10.1007/s11033-021-06611-7.

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15

Provvedi, Roberta, Francesca Boldrin, Francesco Falciani, Giorgio Palù, and Riccardo Manganelli. "Global transcriptional response to vancomycin in Mycobacterium tuberculosis." Microbiology 155, no. 4 (April 1, 2009): 1093–102. http://dx.doi.org/10.1099/mic.0.024802-0.

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In order to gain additional understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify potential targets for new antibacterial drugs, we analysed the variation of the Mycobacterium tuberculosis transcriptional profile in response to inhibitory and subinhibitory concentrations of vancomycin. Our analysis identified 153 genes differentially regulated after exposing bacteria to a concentration of the drug ten times higher than the MIC, and 141 genes differentially expressed when bacteria were growing in a concentration of the drug eightfold lower than the MIC. Hierarchical clustering analysis indicated that the response to these different conditions is different, although with some overlap. This approach allowed us to identify several genes whose products could be involved in the protection from antibiotic stress targeting the envelope and help to confer the basal level of M. tuberculosis resistance to antibacterial drugs, such as Rv2623 (UspA-like), Rv0116c, PE20-PPE31, PspA and proteins related to toxin–antitoxin systems. Moreover, we also demonstrated that the alternative sigma factor σ E confers basal resistance to vancomycin, once again underlining its importance in the physiology of the mycobacterial surface stress response.

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16

Al-Asady, Israa N., and Jassim Fatehi Ali. "Review Article: Virulence Factors of Mycobacterium Tuberculosis." Journal for Research in Applied Sciences and Biotechnology 2, no. 3 (July 8, 2023): 221–37. http://dx.doi.org/10.55544/jrasb.2.3.31.

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Mycobacterium tuberculosis (MTB) causes active TB infections that result in pulmonary tuberculosis (PTB), relapse even after treatment, and latent TB. Tuberculosis is a bacterium airborne pulmonary infectious disease. Extra pulmonary tuberculosis (EPTB) results from an illness which is too severe with Mycobacterium tuberculosis entering into the circulatory system. A really bad situation with further multi-drug TB. In the nation, pulmonary TB is spreading as well as reemerging. Recent findings of an increase in cases in the area pose a mortality burden and infection spread risk. The group of bacteria genetically organisms known as the Mycobacterium tuberculosis complex (MTBC) are accountable for human as well as animal tuberculosis. Among the primary reasons of mortality or morbidity worldwide continues to remain this sickness even now. The mycobacteria infiltrate the host via breathing that is phagocytated by macrophage as they reach the respiratory tract. It may cause the bacteria responsible to be quickly destroyed or cause an aggressive TB disease. Precisely a result of its human immunological reaction, multiple distinct virulence indicators have emerged among MTBC subgroups. The purpose of this research is to discuss the bacterial genes or enzymes that are to be crucial to determining the pathogenicity of MTBC strains through in vivo infections paradigm. As a way to eradicate various illnesses as well as get closer to a future without infections such as tuber emerging medicines or therapies must take into account the virulence aspects of MTBC.

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17

Beaucher, Jocelyn, Sébastien Rodrigue, Pierre-Étienne Jacques, Issar Smith, Ryszard Brzezinski, and Luc Gaudreau. "Novel Mycobacterium tuberculosis anti-σ factor antagonists control σF activity by distinct mechanisms." Molecular Microbiology 45, no. 6 (September 27, 2002): 1527–40. http://dx.doi.org/10.1046/j.1365-2958.2002.03135.x.

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18

Moraes, Eloise Brasil, Letícia Slompo, Amanda Juliane Finardi, Heloisa Paro Pedro da Silveira, Luciana Ruiz, Harrison Magdinier Gomes, Virginia Bodelão Richini, et al. "Tuberculosis associated factors caused by Mycobacterium tuberculosis of the RDRio genotype." Memórias do Instituto Oswaldo Cruz 112, no. 3 (February 16, 2017): 182–87. http://dx.doi.org/10.1590/0074-02760160347.

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19

SÁNCHEZ, VICENTE MARTÍN, FERNANDO ALVAREZ-GUISASOLA, JOAN A. CAYLÁ, and JOSE L. ALVAREZ. "Predictive Factors of Mycobacterium tuberculosis Infection and Pulmonary Tuberculosis in Prisoners." International Journal of Epidemiology 24, no. 3 (1995): 630–36. http://dx.doi.org/10.1093/ije/24.3.630.

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20

Barry, C. "Interpreting cell wall 'virulence factors' of Mycobacterium tuberculosis." Trends in Microbiology 9, no. 5 (May 1, 2001): 237–41. http://dx.doi.org/10.1016/s0966-842x(01)02018-2.

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21

Andarge, Degineh Belachew, Tariku Lambiyo Anticho, Getamesay Mulatu Jara, and Musa Mohammed Ali. "Prevalence of Mycobacterium tuberculosis infection and rifampicin resistance among presumptive tuberculosis cases visiting tuberculosis clinic of Adare General Hospital, Southern Ethiopia." SAGE Open Medicine 9 (January 2021): 205031212110455. http://dx.doi.org/10.1177/20503121211045541.

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Objective: Multidrug-resistant Mycobacterium tuberculosis is a public health threat in resource-limited countries where it is easily disseminated and difficult to control. The aim of this study was to determine the prevalence of tuberculosis, rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis, and associated factors among presumptive tuberculosis cases attending the tuberculosis clinic of Adare General Hospital located in Hawassa city. Methods: A hospital-based cross-sectional study was conducted among 321 tuberculosis suspected patients from April to July 2018. Socio-demographic, environmental, and behavioral data were collected using a structured questionnaire. Sputum specimens were analyzed using GeneXpert. Data entry was made using Epi info version 7 and analyzed by SPSS version 20. Logistic regression models were used to determine the risk factors. A p-value less than 0.05 was taken as a cut point. Results: In this study, the prevalence of Mycobacterium tuberculosis was 98 (30.5%) with 95% confidence interval (25.5–35.8), and the prevalence of rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis among the 98 Mycobacterium tuberculosis confirmed cases was 4 (4.1%). The prevalence of rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis among the tuberculosis suspected patients was 1.24%. Participants who had a history of treatment with anti-tuberculosis drugs were more likely to develop rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis. Conclusions: This study identified relatively high rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis among tuberculosis suspected patients in the study area. Early detection of drug-resistant Mycobacterium tuberculosis should be given enough attention to strengthen the management of tuberculosis cases and improve direct observation therapy short-course and eventually minimize the spread of rifampicin-resistant tuberculosis strain in the community.

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22

Pasechnik, O. A., A. A. Vyazovaya, M. A. Dymova, A. I. Blokh, V. L. Stasenko, M. P. Tatarintseva, and I. V. Mokrousov. "Tuberculosis outcomes related to the Mycobacterium tuberculosis genotype." Russian Journal of Infection and Immunity 9, no. 3-4 (November 15, 2019): 531–38. http://dx.doi.org/10.15789/2220-7619-2019-3-4-531-538.

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Mycobacterium tuberculosis strains of different phylogenetic lineages and genetic families differ in biological properties that determine, to some extent, epidemiological features and clinical manifestation in tuberculosis (TB) patients.The aim of the study was to assess the risk of an adverse outcome of the disease in TB patients caused by various M. tuberculosis genotypes.Materials and methods. A total of 425 patients with respiratory TB were enrolled in this study. They were registered at phthisiatric facilities in the Omsk region from March 2015 to June 2017 period and included: males — 73.1%, mean age 39.9 years, females — 26.9%, mean age 42.0 years. M. tuberculosis culture and drug susceptibility testing and DNA extraction were performed in accordance with standard methods. Strains were assigned to the M. tuberculosis Beijing genotype and its epidemiologically relevant clusters B0/W148 and 94-32 by PCR based detection of specific markers. Non-Beijing strains were subjected to spoligotyping.Results. We found that 66.5% isolates belonged to the Beijing genotype, 12.8% — to LAM, 10.1% — to T, and 4.7% — to the Ural genotype. Multi-drug resistance (MDR) to anti-TB drugs was observed in 195 M. tuberculosis strains (45.9%). Moreover, Beijing genotype was more often isolated from patients with MDR-TB infection (PR = 2.09 (95% CI 1.6–2.74) and TB infection associated with HIV infection (PR = 1.14 (95% CI 1.01–1.31). Lethal outcome was double higher in patients infected with Beijing vs. non-Beijing strains, 28.6% vs. 14.0% (PR = 2.03; 95% CI 1.3–3.17). The risk factors were identified as follows: young age 18–44 years (RR = 1.7; 95% CI 1.18–2.7), co-morbidity with HIV (RR = 5.0; 95% CI 3.39–7.45), multiple (RR = 1.7; 95% CI 1.14–2.55) and extensive drug resistance (RR = 2.57; 95% CI 1.35–4.92), and association with the Beijing genotype (RR = 2.0, 95% CI 1.3–3.17).Conclusion. M. tuberculosis spread in the Omsk region is characterised by significant prevalence of the Beijing genotype, associated with multiple and extensive drug resistance. A significant association of adverse clinical outcomes and various factors, including association with the Beijing genotype, requires development of new approaches in the fight against tuberculosis.

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23

Allan-Blitz, L., M. Ogopotse, J. Billings, C. Modongo, O. Fane, S. Shin, J. Klausner, and N. Zetola. "Factors that influence mycobacterium tuberculosis culture results in patients diagnosed with tuberculosis." Annals of Global Health 81, no. 1 (March 12, 2015): 124. http://dx.doi.org/10.1016/j.aogh.2015.02.787.

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24

van Crevel, Reinout, Tom H. M. Ottenhoff, and Jos W. M. van der Meer. "Innate Immunity to Mycobacterium tuberculosis." Clinical Microbiology Reviews 15, no. 2 (April 2002): 294–309. http://dx.doi.org/10.1128/cmr.15.2.294-309.2002.

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SUMMARY The different manifestations of infection with Mycobacterium tuberculosis reflect the balance between the bacillus and host defense mechanisms. Traditionally, protective immunity to tuberculosis has been ascribed to T-cell-mediated immunity, with CD4+ T cells playing a crucial role. Recent immunological and genetic studies support the long-standing notion that innate immunity is also relevant in tuberculosis. In this review, emphasis is on these natural, innate host defense mechanisms, referring to experimental data (e.g., studies in gene knockout mice) and epidemiological, immunological, and genetic studies in human tuberculosis. The first step in the innate host defense is cellular uptake of M. tuberculosis, which involves different cellular receptors and humoral factors. Toll-like receptors seem to play a crucial role in immune recognition of M. tuberculosis, which is the next step. The subsequent inflammatory response is regulated by production of pro- and anti-inflammatory cytokines and chemokines. Different natural effector mechanisms for killing of M. tuberculosis have now been identified. Finally, the innate host response is necessary for induction of adaptive immunity to M. tuberculosis. These basic mechanisms augment our understanding of disease pathogenesis and clinical course and will be of help in designing adjunctive treatment strategies.

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25

Cousins, Debby. "Mycobacterium bovis: an extraordinary pathogen." Microbiology Australia 25, no. 4 (2004): 15. http://dx.doi.org/10.1071/ma04415.

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Mycobacterium bovis, originally considered to be the precursor of human tuberculosis by ?crossing over? when man first began domesticating animals, is now considered at the opposite end of the evolutionary spectrum. M. bovis belongs in the M. tuberculosis complex, a group of organisms that has, until relatively recently, contained the established pathogens M. tuberculosis, M. africanum, M. bovis (and M. bovis BCG) and M. microti. M. tuberculosis and M. africanum primarily affect humans and M. microti is the main pathogen of voles. M. bovis is the causative organism of bovine tuberculosis, a well known zoonotic disease that can impact on human health, international trade and production. In fact, because of these factors, most developed countries have spent large sums of money attempting to eradicate or control bovine tuberculosis.

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26

Mukamolova, Galina V., Obolbek A. Turapov, Danielle I. Young, Arseny S. Kaprelyants, Douglas B. Kell, and Michael Young. "A family of autocrine growth factors in Mycobacterium tuberculosis." Molecular Microbiology 46, no. 3 (October 31, 2002): 623–35. http://dx.doi.org/10.1046/j.1365-2958.2002.03184.x.

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27

Ali, Mohamed Muhumed, Fitsum Weldegebreal, Getachew Kabew, and Kedir Urgesa. "Rifampicin resistant Mycobacterium tuberculosis and associated factors among presumptive pulmonary tuberculosis patients in Mogadishu, Somalia." SAGE Open Medicine 11 (January 2023): 205031212211486. http://dx.doi.org/10.1177/20503121221148603.

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Background: Multi-drug resistant Mycobacterium tuberculosis is a growing public health problem in developing countries including Somalia. Although, the prevalence of multi-drug resistant tuberculosis among new and retreated cases is high, data on GeneXpert- Mycobacterium tuberculosis/rifampicin-resistant assay, which is a surrogate marker for multidrug resistance, is not well explored in Mogadishu. Objectives: To determine the prevalence of rifampicin-resistant Mycobacterium tuberculosis and its associated factors among presumptive pulmonary tuberculosis patients visiting tuberculosis centers in Mogadishu, Somalia. Methods: A multicenter cross-sectional study was conducted in three tuberculosis treatment centers from March 12 to April 30, 2021. Laboratory professionals collected sputum sample consecutively from presumptive pulmonary tuberculosis participants and performed a GeneXpert assay to determine the rifampicin resistance. Socio-demographic and clinical data were collected using structured questionnaire. Logistic regression analyses were performed to assess factors associated with rifampicin resistance using an adjusted odds ratio at a 95% confidence interval. Statistical significance was considered at a p-value of less than 0.05. Results: A total of 370 presumptive tuberculosis suspects were included; of whom 58.4% were females and the mean age of the participants was 44.3 ± 14 years. Mycobacterium tuberculosis was detected in 63 (17%) (95% confidence interval = 13.2–20.8) suspects. Of these the prevalence of rifampicin-resistant Mycobacterium tuberculosis was 35% (95% confidence interval = 30.2–39.8). Anti-tuberculosis treatment history (adjusted odds ratio = 4.1; 95% confidence interval = 1.91–6.75), monthly income less than $100 USD (adjusted odds ratio = 2.2; 95% confidence interval = 1.77–5.98) and being diagnosed with Asthma (adjusted odds ratio = 2.63; 95% confidence interval = 1.3–7.3) were significantly associated with rifampicin-resistant tuberculosis. Conclusion: A considerable proportion of rifampicin-resistant tuberculosis is reported in these study settings. The strong association between multidrug resistance tuberculosis and patients’ retreatment history of tuberculosis, low income, and co-morbidity with asthma highlights the need for more efforts in tuberculosis treatment and monitoring programs to limit the emergence of multi-drug resistant strain in the study areas.

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28

Mai, Trinh Quynh, Elena Martinez, Ranjeeta Menon, Nguyen Thi Van Anh, Nguyen Tran Hien, Nguyen Huu Lan, Do Chau Giang, et al. "Tuberculosis risk factors and Mycobacterium tuberculosis transmission among HIV-infected patients in Vietnam." Tuberculosis 115 (March 2019): 67–75. http://dx.doi.org/10.1016/j.tube.2019.02.001.

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29

Kukurika, A. V., E. I. Veselova, and A. B. Peregudova. "Genetic Aspects of Mycobacterium Tuberculosis Resistance to New Anti-Tuberculosis Drugs." Tuberculosis and Lung Diseases 101, no. 4 (August 28, 2023): 87–93. http://dx.doi.org/10.58838/2075-1230-2023-101-4-87-93.

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We analyzed 57 publications devoted to study of genetic mechanisms of formation of drug resistance of Mycobacterium tuberculosis to bedaquiline, delamanid, pretomanid, linezolid, and clofazimine. Identification of genetic factors of MTB drug resistance make the basis to search for new targets in development of anti-tuberculosis drugs and methods for drug susceptibility testing.

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30

Gomes de Andrade, Rayanny, Ana Paula Junqueira-Kipnis, and Andre Kipnis. "PROTEASES ASSOCIATED WITH Mycobacterium tuberculosis INFECTION." Revista de Patologia Tropical / Journal of Tropical Pathology 48, no. 1 (April 10, 2019): 1–12. http://dx.doi.org/10.5216/rpt.v48i1.56992.

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Tuberculosis is a contagious infectious disease caused by Mycobacterium tuberculosis, an obligate intracellular bacterium that relies on infection and host to host transmission to survive. In a co-evolution process, the pathogen developed virulence mechanisms to evade the host’s immune system and endure many factors, such as cellular stress for example. One of the strategies used by pathogens to achieve success in their infection is the production of proteases, which are enzymes that cleave peptide bonds between the amino acids in a protein. Proteases are widely distributed in the nature and have different roles that are considered important to the bacteria biological cycle. M. tuberculosis have several protease coding genes in its genome, many of which with unknown function, but several with attributed role in the infection process. This review presents the literature searched between 2014 and 2018 that addressed the roles of the proteases involved in the Mycobacterium tuberculosis infection.

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31

Kenedyanti, Evin, and Lilis Sulistyorini. "Analysis of Mycobacterium tuberculosis and Physical Condition of The House with Incidence Pulmonary Tuberculosis." Jurnal Berkala Epidemiologi 5, no. 2 (October 27, 2017): 152. http://dx.doi.org/10.20473/jbe.v5i22017.152-162.

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Diseases that can be caused by environmental factors one of which is tuberculosis (TB). TB is an infectious disease that most often affects the lung tissue by Mycobacterium tuberculosis. Based on the observation of the condition of the settlement in the district Mulyorejo very crowded and poor sanitation, it may result in environmentally based disease is pulmonary tuberculosis (TB). This study was an observational study, the design of the study is a case-control study. Analysis of the data used are seeing the value OR. The sample was taken by purposive sampling with a sample size of 5 houses pulmonary tuberculosis patients and 10 home instead of pulmonary tuberculosis patients. The collection of data by observation sheet, physical measurements of air quality, and air sampling using Haz-Dust EPAM-5000 models, then dust samples were sent to the Institute of Tropical Disease Airlangga University for examination Mycobacterium tuberculosis bacteria in the air by PCR Aerosol. The results showed Mycobacterium tuberculosis in the air is a risk factor for pulmonary tuberculosis (OR = 2.667) and the physical condition of the house is a risk factor for pulmonary tuberculosis (OR = 2.667). People should improve the physical condition of the house, particularly the addition of mechanical ventilation to facilitate air circulation. For a house whose walls are attached to the neighboring wall can make the air vent on the roof, for further research using more samples to determine the factors that cause Mycobacterium tuberculosis in the home of respondents both patients and non-sufferers.Keywords:physical condition of the home, lung tuberculosis (TB), Mycobacterium tuberculosis

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Waqar Mazhar, Muhammad. "Mycobacterium Tuberculosis, Culturing and PCR Optimization." Annals of Experimental and Molecular Biology 3, no. 1 (2021): 1–5. http://dx.doi.org/10.23880/aemb-16000108.

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The genus Acinetobacter baumannii has undergone substantial taxonomic modifications over the last 30 years. Acinetobacter baumannii is one of the most important representatives of the genus and pathogen for healthcare facilities globally. Over the last 15 years, its clinical significance shows that it has the ability to acquire resistance against antibiotics in this threatening antibiotic era. Naturally A.baumannii can easily be isolated from different sources throughout whole world, found mostly in water, soil, sputum and many healthcare environments, is a non-fermenting, non-spore forming and gram negative coccobacilli. Pneumonia caused by MDR strains of Acinetobacter baumannii creating serious issues for Physicians to treat it properly. Risk factor for two types of patients recognized to pneumonia infection Acinetobacter baumannii hospital associated pneumonia (AHAP) and Acinetobacter baumannii ventilator associated pneumonia (AVAP), by univariate analysis prior to ceftazidime treatment. It is to be reported that potential risk factors for AVAP includes, imipenem resistance, long duration of hospital stay and fluoroquinolones exposure.

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Madani, Hasna Aldisa, and Adi Imam Cahyadi. "Potential Transmission of Zoonotic Tuberculosis Disease from Livestock to Humans." Indonesian Bulletin of Animal and Veterinary Sciences 32, no. 2 (August 22, 2022): 59–68. http://dx.doi.org/10.14334/wartazoa.v32i2.2923.

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Zoonotic Tuberculosis (Ztb) is caused by member of group bacteria called Mycobacterium tuberculosis complex which can attack animals as reservoirs and is zoonotic so that it can be transmitted and infected humans. This paper aims to review about zoonotic tuberculosis which includes: causative agents, modes of transmission, risk factors and prevention of Ztb transmission from livestock to humans. Based on reviewing 47 literatures, it shows that zoonotic tuberculosis in livestock can be caused by Mycobacterium bovis, Mycobacterium caprae and Mycobacterium orygis. The disease is transmitted by inhalation and oral routes. The most common risk factors are types of livestock rearing, age of livestock and population or herds size. There are several measures to prevent Ztb transmitted from livestock to humans, such as improving the good maintenance management, implementation of routine surveillance program, increasing vaccination coverage and other preventive measures by taking into account all risk factors that can increase the incidence and transmission of Ztb.

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Thakur, Krishan Gopal, Ravi Kumar Jaiswal, Jinal K. Shukla, T. Praveena, and B. Gopal. "Over-expression and purification strategies for recombinant multi-protein oligomers: A case study of Mycobacterium tuberculosis σ/anti-σ factor protein complexes." Protein Expression and Purification 74, no. 2 (December 2010): 223–30. http://dx.doi.org/10.1016/j.pep.2010.06.018.

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Ikram Hasanuddin, Abdi Dzul, Nanang Roswita, and Ivan Virnanda Amu. "Immune Response toward Mycobacterium Tuberculosis Infection." Green Medical Journal 2, no. 2 (August 30, 2020): 77–87. http://dx.doi.org/10.33096/gmj.v2i2.47.

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Understanding the human immune response toward Mycobacterium tuberculosis infection is important for controlling its infection. Its transmission through the air consists of "droplets nuclei" containing TB bacilli. After initial infection, the human body will provide diverse immune responses and will determine different clinico-histopathologic finding. This response starts from innate immunity that consists of phagocytosis by distal alveolar macrophages or nasal microfold cells, then will be continued by dendritic cells to be transferred to mediastinal lymph nodes to induced adaptive immune responses. This response is mediated by cells through IFN- γ signaling which will enhance phagocytosis. If this response is effective, there will be a latent infection with an initial histopathological finding of caseosa granulomas and predominantly followed by chronic granulomas. In a few cases, it can be reactivated via the IL-10 activation pathway and exogenous factors, it will induce a great adaptive immune reaction and provide more severe clinico-histopathological manifestation. The existence of the human body's immune response to Mycobacterium tuberculosis, etiher innate or adaptive immunity will determine the clinical course and pathology that will occur.

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Jaiswal, Ravi K., Tangirala Surya Prabha, Gowravaram Manjeera, and Balasubramanian Gopal. "Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of σ-factor activity by proteolysis." Nucleic Acids Research 41, no. 5 (January 10, 2013): 3414–23. http://dx.doi.org/10.1093/nar/gks1468.

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Lestari Muslimah, Diah Dwi. "Physical Environmental Factors and Its Association with the Existence of Mycobacterium Tuberculosis: A Study in The Working Region of Perak Timur Public Health Center." JURNAL KESEHATAN LINGKUNGAN 11, no. 1 (February 1, 2019): 26. http://dx.doi.org/10.20473/jkl.v11i1.2019.26-34.

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In 2017, Surabaya District Health Office reported an increasing number of new cases of pulmonary tuberculosis in the working region of of East Perak Surabaya Public Health Center (Puskesmas) and was reported as the highest rates of tuberculosis cases in Surabaya. Pulmonary tuberculosis can be transmitted through ambient air contamination initiated by the presence of Mycobacterium tuberculosis. This study aims to determine the association of physical environmental factors (temperature, humidity, lighting, ventilations’ size, floor materials, walls, ceilings, and density) in the presence of Mycobacterium tuberculosis in the air. This research is an observational analytic study with case control study design. The study sample consisted of 21 households/realtives of patients diagnosed with Pulmonary TB positive. The data was obtained from completed questionnaires by respondents, direct observation and laboratory examination of the presence of Mycobacterium tuberculosis in the air. Data analysis was conducted by Chi-square test supported by Fisher's Exact Test test. The results showed that the significant association between physical environment variables of temperature variables (p-value= 0,000), humidity (p-value= 0,000), lighting (p = 0,000), with the existence of mycobacterium tuberculosis inside of the room. While insignificant association was detected for the variables of ventilation (p = 0.397), floor materials (p = 0.229), the walls materials (p = 0.338), the ceiling condition (p = 0.331), and the dwellers density (p = 0.611), with the presence of Mycobacterium tuberculosis in the air of the common room this current study concludes that there is a significant association between temperature, humidity, and illumination with the presence of Mycobacterium tuberculosis in ambient of common room. Transmission of tuberculosis can be eliminated by using face masks, Despite the previous satisfied level of knowledge, the family behavior and practices when in contact with patients were insufficient to prevent pulmonary TB transmission.

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Salova, A. L., O. G. Chelnokova, L. I. Mozzhukhina, and T. A. Kogut. "Mycobacterium tuberculosis Infection and the development of laryngeal stenosis in children — is there a relationship?" CHILDREN INFECTIONS 18, no. 3 (October 8, 2019): 57–60. http://dx.doi.org/10.22627/2072-8107-2019-18-3-57-60.

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The aim is to study the relationship of Mycobacterium tuberculosis infection and the development of laryngeal stenosis (croup) in children. 250 children with croup aged from 6 months to 8 years were examined.It was found that infection with Mycobacterium tuberculosis in children with laryngeal stenosis (croup) developed at the age of under 4 years. The first episode of croup coincided in 90% of cases with the early period of primary infection with Mycobacterium tuberculosis. A high proportion of close contact with adult tuberculosis patients reached 35% in patients with recurrent laryngeal stenosis (croup). The incidence of tuberculosis among children with repeated episodes of croup was 30%. Anti-TB therapy for latent tuberculosis infection or local forms of tuberculosis led to the cessation of repeated episodes of croup in 85% of cases. Infection with Mycobacterium tuberculosis and active tuberculosis infection is considered as one of the factors contributing to the recurrent course of laryngeal stenosis in children.

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Søborg, Bolette, Aase Bengaard Andersen, Mads Melbye, Jan Wohlfahrt, Mikael Andersson, Robert Biggar, Karin Ladefoged, Vibeke Ostergaard Thomsen, and Anders Koch. "Risk factors for Mycobacterium tuberculosis infection among children in Greenland." Bulletin of the World Health Organization 89, no. 10 (October 1, 2011): 741–48. http://dx.doi.org/10.2471/blt.10.084152.

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Sachdeva, Preeti, Richa Misra, Anil K. Tyagi, and Yogendra Singh. "The sigma factors of Mycobacterium tuberculosis: regulation of the regulators." FEBS Journal 277, no. 3 (November 27, 2009): 605–26. http://dx.doi.org/10.1111/j.1742-4658.2009.07479.x.

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Hett, Erik C., Michael C. Chao, Adrie J. Steyn, Sarah M. Fortune, Lynn L. Deng, and Eric J. Rubin. "A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis." Molecular Microbiology 66, no. 3 (November 2007): 658–68. http://dx.doi.org/10.1111/j.1365-2958.2007.05945.x.

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Prozorov, A. A., I. A. Fedorova, O. B. Bekker, and V. N. Danilenko. "The virulence factors of Mycobacterium tuberculosis: Genetic control, new conceptions." Russian Journal of Genetics 50, no. 8 (August 2014): 775–97. http://dx.doi.org/10.1134/s1022795414080055.

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Klote, M. M., L. Y. Agodoa, and K. C. Abbott. "Risk factors for Mycobacterium tuberculosis in US chronic dialysis patients." Nephrology Dialysis Transplantation 21, no. 11 (September 12, 2006): 3287–92. http://dx.doi.org/10.1093/ndt/gfl488.

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Berisio, Rita, and Alessia Ruggiero. "Virulence Factors in Mycobacterium tuberculosis Infection: Structural and Functional Studies." Biomolecules 13, no. 8 (July 31, 2023): 1201. http://dx.doi.org/10.3390/biom13081201.

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Park, Sehoon, Soojin Lee, Yaerim Kim, Yeonhee Lee, Min Woo Kang, Semin Cho, Kyungdo Han, et al. "Association of CKD with Incident Tuberculosis." Clinical Journal of the American Society of Nephrology 14, no. 7 (June 6, 2019): 1002–10. http://dx.doi.org/10.2215/cjn.14471218.

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Background and objectivesThe incidence and risk of Mycobacterium tuberculosis in people with predialysis CKD has rarely been studied, although CKD prevalence is increasing in certain countries where Mycobacterium tuberculosis is endemic. We aimed to investigate the association between predialysis CKD and active Mycobacterium tuberculosis risks in a nation with moderate Mycobacterium tuberculosis risk.Design, setting, participants, & measurementsIn this nationwide retrospective cohort study, we reviewed the National Health Insurance Database of Korea, screening 17,020,339 people who received a national health screening two or more times from 2012 to 2016. Predialysis CKD was identified with consecutive laboratory results indicative of CKD (e.g., persistent eGFR <60 ml/min per 1.73 m2 or dipstick albuminuria). People with preexisting active Mycobacterium tuberculosis or kidney replacement therapy were excluded. A 1:1 matched control group without CKD was included with matching for age, sex, low-income status, and smoking history. The risk of incident active Mycobacterium tuberculosis, identified in the claims database, was assessed by the multivariable Cox regression model, which included both matched and unmatched variables (e.g., body mass index, diabetes, hypertension, places of residence, and other comorbidities).ResultsWe included 408,873 people with predialysis CKD and the same number of controls. We identified 1704 patients with active Mycobacterium tuberculosis (incidence rate =137.5/100,000 person-years) in the predialysis CKD group and 1518 patients with active Mycobacterium tuberculosis (incidence rate =121.9/100,000 person-years) in the matched controls. The active Mycobacterium tuberculosis risk was significantly higher in the predialysis CKD group (adjusted hazard ratio, 1.21; 95% confidence interval, 1.13 to 1.30). The risk factors for active Mycobacterium tuberculosis among the predialysis CKD group were old age, men, current smoking, low income, underlying diabetes, chronic obstructive pulmonary disease, and Kidney Disease Improving Global Outcomes CKD stage 1 (eGFR≥90 ml/min per 1.73 m2 with persistent albuminuria) or stage 4/5 without dialysis (eGFR<30 ml/min per 1.73 m2).ConclusionsIn the Korean population, the incidence of active Mycobacterium tuberculosis was higher in people with versus without predialysis CKD.

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Agustina, Betty, Cissy Kartasasmita, and Dany Hilmanto. "Comparison of GeneXpert MTB to Mycobacterium tuberculosis culture in children with tuberculosis." Paediatrica Indonesiana 59, no. 3 (May 2, 2019): 113–8. http://dx.doi.org/10.14238/pi59.3.2019.113-8.

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Background Diagnosing tuberculosis (TB) in children is difficult. Typical methods take a long time to achieve results, or have a low sensitivity. GeneXpert is a nucleic acid amplification test used to identify Mycobacterium tuberculosis bacteria (MTB) in only 2 hours. Objective To compare the sensitivity and specificity of GeneXpert MTB to MTB culture in children with TB, and to assess factors associated with GeneXpert MTB test in predicting which children were likely to have positive results. Methods This descriptive, analytical study was done in children with suspected TB, aged 1 month to 18 years in Hasan Sadikin Hospital, Bandung, West Java, from January 2016 to December 2017. The data were taken from the medical records and included age, gender, nutritional status, symptoms of TB, chest x-ray, and tuberculin test results. The GeneXpert MTB test was compared to cultures from the same patient, with regards to sensitivity, specificity, and agreement using Kappa index. We analyzed factors associated to GeneXpert MTB test using logistic regression analysis. Results From 454 inpatients and 1,750 outpatients with suspected TB, there were 251 children who were tested by MTB culture and 722 children tested by GeneXpert MTB. Of the 70 cases who met the inclusion criteria and underwent both tests, factors associated with positive GeneXpert MTB results were age 10 to 18 years, female gender, and positive tuberculin skin test (TST). The GeneXpert MTB test showed sensitivity 78.9% (95%CI 56.7 to 91.5) and specificity 86.3% (95%CI 74.3 to 93.2), with accuracy of 84.3% (95%CI 74 to 91), and agreement value of ƙ=0.62 (95%CI 41.6 to 82.7). Conclusion Specificity of GeneXpert MTB is higher than its sensitivity compared to TB cultures in children. The tests were in good agreement. Age 10 to 18 years had the strongest association with positive GeneXpert MTB results.

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Bespyatykh, Julia, Egor Shitikov, Dmitry Bespiatykh, Andrei Guliaev, Ksenia Klimina, Vladimir Veselovsky, Georgij Arapidi, et al. "Metabolic Changes of Mycobacterium tuberculosis during the Anti-Tuberculosis Therapy." Pathogens 9, no. 2 (February 18, 2020): 131. http://dx.doi.org/10.3390/pathogens9020131.

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Tuberculosis, caused by Mycobacterium tuberculosis complex bacteria, remains one of the most pressing health problems. Despite the general trend towards reduction of the disease incidence rate, the situation remains extremely tense due to the distribution of the resistant forms. Most often, these strains emerge through the intra-host microevolution of the pathogen during treatment failure. In the present study, the focus was on three serial clinical isolates of Mycobacterium tuberculosis Beijing B0/W148 cluster from one patient with pulmonary tuberculosis, to evaluate their changes in metabolism during anti-tuberculosis therapy. Using whole genome sequencing (WGS), 9 polymorphisms were determined, which occurred in a stepwise or transient manner during treatment and were linked to the resistance (GyrA D94A; inhA t-8a) or virulence. The effect of the inhA t-8a mutation was confirmed on both proteomic and transcriptomic levels. Additionally, the amount of RpsL protein, which is a target of anti-tuberculosis drugs, was reduced. At the systemic level, profound changes in metabolism, linked to the evolution of the pathogen in the host and the effects of therapy, were documented. An overabundance of the FAS-II system proteins (HtdX, HtdY) and expression changes in the virulence factors have been observed at the RNA and protein levels.

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Wang, Jann-Yuan, Po-Ren Hsueh, Yuang-Shuang Liaw, Wen-Yi Shau, Pan-Chyr Yang, Kwen-Tay Luh, and Li-Na Lee. "Mycobacterium tuberculosis inducing disseminated intravascular coagulation." Thrombosis and Haemostasis 93, no. 04 (2005): 729–34. http://dx.doi.org/10.1160/th04-09-0562.

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SummaryDisseminated intravascular coagulation (DIC) can develop infrequently in patients with tuberculosis and has a very high mortality rate. We conducted a retrospective study to evaluate the incidence of tuberculosis-induced DIC and to investigate the clinical manifestation, outcome, and prognostic factors of such patients. From January 2002 to December 2003, all culture-proven tuberculosis patients who developed DIC before starting anti-tuberculosis treatments were selected for this study. Patients who had other clinical conditions or were infected by other pathogens that may have been responsible for their DIC were excluded. Survival analysis was performed for each variable with possible prognostic significance. Our results showed that 27 (3.2%) out of the 833 patients with culture-proven tuberculosis had tuberculosis-induced DIC with a mortality rate of 63.0%. The most common clinical manifestations were fever (63.0%) and multiple patches of pulmonary consolidation (59.3%). Seven (25.9%) patients had disseminated tuberculosis. Twelve (44.4%) developed acute respiratory distress syndrome and three (11.1%) were associated with hemophagocytosis. Twenty-four (88.9%) patients had findings that were unusual for an acute bacterial infection, such as positive acid-fast smear, miliary pulmonary lesions, lymphocytotic exudative pleural effusion, and mediastinal lymphadenopathy. Early anti-tuberculosis treatment significantly improved survival. In conclusion, tuberculosis can cause DIC. Patients with non-miliary, non-disseminated tuberculosis could also develop the rare clinical manifestation. Since the prognosis was very poor in patients not treated at an early stage, a high index of suspicion is required, especially in those with clinical findings suggestive of tuberculosis.

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Videnovic-Ivanov, Jelica, Violeta Vucinic-Mihailovic, and Dragan Mandaric. "The impact of resistant strains of mycobacterium tuberculosis on relapse of tuberculosis." Medical review 59, no. 11-12 (2006): 522–25. http://dx.doi.org/10.2298/mpns0612522v.

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Introduction. Relapses of tuberculosis are fairly rare nowdays and they represent the onset of tuberculosis two, or more than two years after completion of previous treatment. Material and Methods. In the previous period, relapses of tuberculosis occurred in 141 patients (87 male and 54 female). Their mean age was 46.2 years. Results. Relapses of tuberculosis occurred after 11.3 years, on average. All patients presented with pulmonary tuberculosis, and two patients also had pulmonary and extrapulmonary tuberculosis(bones). Resistance was one of the statistically significant factors for relapse of tuberculosis. Resistance to one antituberculotic agent was most common - 8 patients, resistance to two drugs - 4 patients, resistance to three drugs - 4 patients, resistance to four drugs in 5 patients. Due to these findings on resistant strains of mycobacterium tuberculosis, a huge number of patients with relapses of tuberculosis had full recovery and completed the treatment. Conclusion. The importance of resistant strains of mycobacterium tuberculosis is really huge in our conditions. The findings of these resistant strains of mycobacterium tuberculosis and adequate medical treatment are obligatory nowadays. .

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Cole, Stewart T. "Inhibiting Mycobacterium tuberculosis within and without." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1707 (November 5, 2016): 20150506. http://dx.doi.org/10.1098/rstb.2015.0506.

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Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis . Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials. Attempts to find new lead compounds employing target-based screens were unsuccessful as the leads were inactive against M. tuberculosis . Greater success was achieved using phenotypic screening against live tubercle bacilli and this gave rise to the drugs bedaquiline, pretomanid and delamanid, currently in phase III trials. Subsequent phenotypic screens also uncovered new leads and targets but several of these targets proved to be promiscuous and inhibited by a variety of seemingly unrelated pharmacophores. This setback sparked an interest in alternative screening approaches that mimic the disease state more accurately. Foremost among these were cell-based screens, often involving macrophages, as these should reflect the bacterium's niche in the host more faithfully. A major advantage of this approach is its ability to uncover functions that are central to infection but not necessarily required for growth in vitro . For instance, inhibition of virulence functions mediated by the ESX-1 secretion system severely attenuates intracellular M. tuberculosis , preventing intercellular spread and ultimately limiting tissue damage. Cell-based screens have highlighted the druggability of energy production via the electron transport chain and cholesterol metabolism. Here, I review the scientific progress and the pipeline, but warn against over-optimism due to the lack of industrial commitment for tuberculosis drug development and other socio-economic factors. This article is part of the themed issue ‘The new bacteriology’.

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