Tuberculosis RSS feed: Current Issue. Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism. Areas covered include: immunology immunogenetics pathogenetics microbiology microbial physiology pathogenesis pathology molecular epidemiology diagnostics vaccine development drug resistance The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis. To view the benefits of Online Submission please click here. http://www.tuberculosisjournal.com/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Tuberculosis1472-9792921January 2012 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.tuberculosisjournal.com/article/PIIS1472979212000054/abstract?rss=yesEditorial Board10.1016/S1472-9792(12)00005-4Tuberculosis 92, 1 (2012)2012-01-01Tuberculosis2012-01-01921S1472-9792(12)X0002-7iihttp://www.tuberculosisjournal.com/article/PIIS1472979211000977/abstract?rss=yesSummary: Pyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy. Despite routine use for nearly forty years uncertainty remains regarding the most appropriate PZA dosage for children. In view of this uncertainty literature relating to the efficacy and pharmacokinetics of PZA in children treated for tuberculosis and in adult volunteers and patients was reviewed. Making use of the PZA maximum concentration (Cmax) following various PZA dosages in different groups straight line regression of concentration on dosage was fitted through the origin by least squares and weighted for the numbers of subjects. The fitted line offers an approximation of the likely PZA Cmax that would result from a particular dosage. The slopes of Cmax/dosage of the fitted lines are 1.32 (SE 0.099) for paediatric patients, 1.36 (SE 0.051) for adult volunteers and 1.35 (SE 0.037) for adult patients; there is little difference between the Cmax concentrations achieved in children and adults, whether patients or healthy volunteers, following various mg/kg body weight dosages, suggesting that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar Cmax. Children can receive the same mg/kg body weight PZA dosage as adults.Highlights: ► The literature describing the pharmacokinetics of PZA in children and adults is reviewed. ► The maximum serum concentrations of PZA reached in children following a range of dosages are compared to those reached in adults after the same dosages. ► The slopes of Cmax/dosage for paediatric patients (1.32; SE 0.099), adult volunteers (1.36; SE 0.037) and adult patients (1.35; SE 0.051) did not differ. ► Children receiving the same PZA dosage as adults will reach similar PZA serum concentrations.Pyrazinamide pharmacokinetics and efficacy in adults and childrenP.R. Donald, J.S. Maritz, A.H. Diacon10.1016/j.tube.2011.05.006Tuberculosis 92, 1 (2012)2011-07-27Tuberculosis2011-07-27921S1472-9792(12)X0002-7Review Articles18http://www.tuberculosisjournal.com/article/PIIS1472979211002125/abstract?rss=yesSummary: Childhood multidrug-resistant tuberculosis (MDR-TB) is an emerging global epidemic. With the imminent roll-out of rapid molecular diagnostic tests, more children are likely to be identified and require treatment. As MDR-TB is resistant to the most effective first-line drugs, clinicians will have to rely on second-line medications which are less effective and often associated with more pronounced adverse effects than first-line therapy. Despite the fact that most of these agents were discovered many years ago, robust information is lacking regarding their pharmacokinetic and pharmacodynamic properties, adverse effects and drug interactions, especially in children. Children differ from adults in the way that drugs are administered, the manner in which they are metabolised and in the adverse effects experienced. The interaction of these drugs with human immunodeficiency virus infection and antiretroviral therapy is also poorly documented. This article reviews the available second-line drugs currently used in the treatment of MDR-TB in children and discusses medication properties and adverse effects while potential interactions with antiretroviral therapy are explored.Paediatric use of second-line anti-tuberculosis agents: A reviewJames A. Seddon, Anneke C. Hesseling, Ben J. Marais, Helen McIlleron, Charles A. Peloquin, Peter R. Donald, H. Simon Schaaf10.1016/j.tube.2011.11.001Tuberculosis 92, 1 (2012)2011-11-28Tuberculosis2011-11-28921S1472-9792(12)X0002-7Review Articles917http://www.tuberculosisjournal.com/article/PIIS147297921100151X/abstract?rss=yesSummary: Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected patients, and is the leading cause of mortality among HIV-infected patients. Genetic susceptibility to TB in HIV negative subjects is well documented. Since coinfections can influence the way in which immune system respond to different pathogens, genetic susceptibility to TB in HIV patients might also change. Studies from India and other parts of the world have shown that genetic susceptibility to TB is influenced by HIV infection. In the present review, we emphasize the role of genetic factors in determining susceptibility to HIV infection, disease progression and development of TB in HIV-infected patients. Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients. However, the results are inconclusive and larger well-defined studies with precise clinical data are required to validate these associations. Apart from candidate gene approach, genome-wide association studies are also needed to unravel the unknown or to establish the previously reported genetic associations with HIV associated TB. Despite the preliminary status of the reported associations, it is becoming clear that susceptibility to development of TB in HIV patients is influenced by both environmental and genetic components. Understanding the genetic and immunologic factors that influence susceptibility to TB in HIV patients could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease.Immunogenetics of HIV and HIV associated tuberculosisS. Raghavan, K. Alagarasu, P. Selvaraj10.1016/j.tube.2011.08.004Tuberculosis 92, 1 (2012)2011-09-23Tuberculosis2011-09-23921S1472-9792(12)X0002-7Review Articles1830http://www.tuberculosisjournal.com/article/PIIS1472979211001612/abstract?rss=yesSummary: Development of novel diagnostics for tuberculosis has so far been governed by the clinical requirement of improving the detection of patients with paucibacillary forms of the disease. For this aim, serological assays have been evaluated using several antigens, but were found insufficiently sensitive, because antibody production associates with the bacterial load of the disease. Consequently, detection of antibodies against a relatively small number of selected well-defined antigens has a much higher sensitivity for sputum smear-positive pulmonary disease in adult HIV-negative patients. They are the most active in generating and spreading aerosols containing live tubercle bacilli, but their detection is often delayed, thus perpetuating the transmission of the infection and disease in the population. High volume throughput serological screening of clinical suspects with mild clinical symptoms may help to achieve diagnosis earlier, than currently used procedures. Such expanded testing could be done more efficiently in laboratories, than at ‘points-of-care’ and at a lower cost than other tests. The feasibility of this approach towards reducing the delayed diagnosis of the most infectious cases of pulmonary tuberculosis needs to be ascertained in prospective diagnostic trials, in populations at a high risk. Reducing the transmission of tuberculosis is of key importance for achieving its continued decline and therefore it is proposed, that the aims of serological screening should shift from clinical to public health priorities.Serodiagnosis of tuberculosis: Due to shift trackJuraj Ivanyi10.1016/j.tube.2011.09.001Tuberculosis 92, 1 (2012)2011-09-19Tuberculosis2011-09-19921S1472-9792(12)X0002-7Review Articles3137http://www.tuberculosisjournal.com/article/PIIS1472979211001661/abstract?rss=yesSummary: Lipoarabinomannan (LAM) is a critical virulence factor in the pathogenesis of Mycobacterium tuberculosis, the causative agent of tuberculosis. LAM is secreted in urine and serum from infected patients and is being studied as a potential diagnostic indicator for the disease. Herein, we present a novel ultra-sensitive and specific detection strategy for monomeric LAM based on its amphiphilic nature and consequent interaction with supported lipid bilayers. Our strategy involves the capture of LAM on waveguides functionalized with membrane mimetic architectures, followed by detection with a fluorescently labeled polyclonal antibody. This approach offers ultra-sensitive detection of lipoarabinomannan (10 fM, within 15 min) and may be extended to other amphiphilic markers. We also show that chemical deacylation of LAM completely abrogates its association with the supported lipid bilayers. The loss of signal using the waveguide assay for deacylated LAM, as well as atomic force microscopy (AFM) images that show no change in height upon addition of deacylated LAM support this hypothesis. Mass spectrometry of chemically deacylated LAM indicates the presence of LAM-specific carbohydrate chains, which maintain antigenicity in immunoassays. Further, we have developed the first three-dimensional structural model of mannose-capped LAM that provides insights into the orientation of LAM on supported lipid bilayers.Understanding the interaction of Lipoarabinomannan with membrane mimetic architecturesHarshini Mukundan, Dominique N. Price, Matthew Goertz, Ramakrishnan Parthasarathi, Gabriel A. Montaño, Sandeep Kumar, Matthew R. Scholfield, Aaron S. Anderson, S. Gnanakaran, Srinivas Iyer, Jurgen Schmidt, Basil I. Swanson10.1016/j.tube.2011.09.006Tuberculosis 92, 1 (2012)2011-10-28Tuberculosis2011-10-28921S1472-9792(12)X0002-7Molecular Aspects3847http://www.tuberculosisjournal.com/article/PIIS147297921100165X/abstract?rss=yesSummary: The extracytoplasmic function (ECF) sigma factor SigC has been implicated in the pathogenesis of Mycobacterium tuberculosis but control of its expression and activity is poorly understood. No proteins that interact with SigC have been detected leading to the suggestion that this sigma factor may be primarily controlled at the level of transcription. It has been suggested that SigC may be autoregulatory and a role has also been proposed for SigF in the expression of sigC. In this study we identified two promoters that were active under standard growth conditions by a combination of transcript start site mapping and promoter-lacZ fusion assays. The dominant promoter, P1, closely resembled mycobacterial SigA-dependent promoters, and introduction of a single base change at the conserved A of the −10 region eliminated promoter activity. Although the sequence of the other, P2, closely resembled the reported SigC consensus motifs, expression directed by this promoter was unaltered in a ΔsigC mutant strain, or in strains defective in other ECF sigma factors for which some similarity in consensus sequences was apparent. Comparison of the effects of different changes in the −10 region suggested that the P2 promoter was most likely recognised by SigA.Mycobacterium tuberculosis H37Rv sigC is expressed from two promoters but is not auto-regulatoryAnchi Chang, Katherine L. Smollett, Krishna K. Gopaul, Bosco H.Y. Chan, Elaine O. Davis10.1016/j.tube.2011.09.005Tuberculosis 92, 1 (2012)2011-10-19Tuberculosis2011-10-19921S1472-9792(12)X0002-7Molecular Aspects4855http://www.tuberculosisjournal.com/article/PIIS1472979211001685/abstract?rss=yesSummary: A major threat to tuberculosis (TB) control programs is the emergence of drug resistant Mycobacterium tuberculosis strains that cause TB that cannot be cured by standard anti-TB drug regimens. Because few data exist on MDR-TB in this region of the country, we performed an epidemiologic study that combined conventional and molecular analysis of MDR-TB cases from Rio Grande do Sul (RS) that were diagnosed in this period and included cases that were under treatment with second line drug schemes. Included were 121 MDR cases and sequencing of rpoB and katG showed that 106 (87.6%) strains were mutated in rpoB and 97 (80.2%) in katG. Spoligotyping demonstrated that the LAM genotype was predominant (n = 70, 57.8%) and included the largest group composed by 22 (18.1%) strains with the LAM5 ST93 genotype. Other main genotypes belonged to the families T (n = 22, 18.2%), U family (n = 16, 13.2%), Haarlem (n = 5, 4.1%) and X (n = 1, 0.8%). Genotyping by IS6110-RFLP analysis showed 51 distinct fingerprints, 38 (31.4%) of these observed only once and the other 13 patterns being shared among the rest of the isolates (n = 83, 68.6%). Among the 22 strains that were LAM5 ST93, only two had different IS6110-RFLP genotypes. In conclusion, there exists a high degree of M. Tuberculosis genotype clustering among MDR-TB cases in Rio Grande do Sul. Moreover, we observed a large MDR-TB outbreak.Characteristics of multidrug-resistant Mycobacterium tuberculosis in southern BrazilPaulo F. Perizzolo, Elis R. Dalla Costa, Andrezza W. Ribeiro, Fernanda S. Spies, Marta O. Ribeiro, Cláudia F. Dias, Gisela Unis, Pedro Almeida da Silva, Harrison M. Gomes, Philip N. Suffys, Maria Lucia R. Rossetti10.1016/j.tube.2011.09.008Tuberculosis 92, 1 (2012)2011-10-17Tuberculosis2011-10-17921S1472-9792(12)X0002-7Molecular Aspects5659http://www.tuberculosisjournal.com/article/PIIS1472979211001703/abstract?rss=yesSummary: Iron acquisition is essential for Mycobacterium tuberculosis (Mtb) virulence. Understanding the molecular mechanisms used by Mtb to scavenge iron during infection might reveal new targets for antimicrobial development. Rv2895c, a homolog of ViuB from Vibrio cholerae has been postulated to be involved in iron-siderophore uptake and utilization in Mtb. This study examines the requirement of Rv2895c for adaptation of Mtb to iron limitation. We show that Rv2895c is dispensable for normal replication of Mtb in iron deficient conditions and in human macrophages. Thus, contrary to the predictions of sequence analysis and in-vitro studies the genetic evidence indicates that in normal conditions Rv2895c is not required for iron acquisition in Mtb.Examining the role of Rv2895c (ViuB) in iron acquisition in Mycobacterium tuberculosisSujatha M. Santhanagopalan, G. Marcela Rodriguez10.1016/j.tube.2011.09.010Tuberculosis 92, 1 (2012)2011-10-20Tuberculosis2011-10-20921S1472-9792(12)X0002-7Mechanisms of Pathogenesis6062http://www.tuberculosisjournal.com/article/PIIS1472979211002150/abstract?rss=yesSummary: Tuberculous pleurisy (TBP) is a frequent extrapulmonary manifestation characterized by the accumulation of inflammatory cells that can sometimes be spontaneously self-cured. To achieve a greater insight into T cells at a local site, we systematically characterized and compared the numbers of antigen-specific T cells responding to BCG- or MTB-specific antigens. Our results showed that significantly higher levels of Th1 cytokines were produced by pleural fluid cells (PFCs) than PBMCs following stimulation with BCG or peptides from Mycobacterium tuberculosis (MTB)-specific antigens, ESAT-6 and CFP-10. The proportions of Th1 cells producing IL-2 alone or IL-2 and TNF-α were higher than those producing IFN-γ alone, following stimulation with ESAT-6 or CFP-10 peptides. The cells responding to BCG, ESAT-6 and CFP-10 displayed a CD45RA−CCR7−CD62L−CD27− effector/effector memory phenotype. The percentages and median fluorescence intensity (MFI) of polyfunctional CD4+ T cells were significantly higher following stimulation with peptides from ESAT-6 or CFP-10 than BCG. Our results demonstrated that significantly higher levels of polyfunctional CD4+ T cells for the epitopes of ESAT-6 or CFP-10 in PFCs may play an important role in the local control of tuberculosis (TB) infection.Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisyLi Li, Dan Qiao, Qin Li, Xianlan Zhang, Suihua Lao, Changyou Wu10.1016/j.tube.2011.11.004Tuberculosis 92, 1 (2012)2011-12-07Tuberculosis2011-12-07921S1472-9792(12)X0002-7Immunological Aspects6371http://www.tuberculosisjournal.com/article/PIIS1472979211000965/abstract?rss=yesSummary: Kinase targets are being pursued in a variety of diseases beyond cancer, including immune and metabolic as well as viral, parasitic, fungal and bacterial. In particular, there is a relatively recent interest in kinase and ATP-binding targets in Mycobacterium tuberculosis in order to identify inhibitors and potential drugs for essential proteins that are not targeted by current drug regimens. Herein, we report the high throughput screening results for a targeted library of approximately 26,000 compounds that was designed based on current kinase inhibitor scaffolds and known kinase binding sites. The phenotypic data presented herein may form the basis for selecting scaffolds/compounds for further enzymatic screens against specific kinase or other ATP-binding targets in Mycobacterium tuberculosis based on the apparent activity against the whole bacteria in vitro.High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37RvRobert C. Reynolds, Subramaniam Ananthan, Ellen Faaleolea, Judith V. Hobrath, Cecil D. Kwong, Clinton Maddox, Lynn Rasmussen, Melinda I. Sosa, Elizabeth Thammasuvimol, E. Lucile White, Wei Zhang, John A. Secrist10.1016/j.tube.2011.05.005Tuberculosis 92, 1 (2012)2011-06-27Tuberculosis2011-06-27921S1472-9792(12)X0002-7Drug Discovery and Resistance7283http://www.tuberculosisjournal.com/article/PIIS1472979211001624/abstract?rss=yesSummary: Pyrazinamide is one of the most important drugs in the treatment of latent Mycobacterium tuberculosis infection. The emergence of strains resistant to pyrazinamide represents an important public health problem, as both first- and second-line treatment regimens include pyrazinamide. The accepted mechanism of action states that after the conversion of pyrazinamide into pyrazinoic acid by the bacterial pyrazinamidase enzyme, the drug is expelled from the bacteria by an efflux pump. The pyrazinoic acid is protonated in the extracellular environment and then re-enters the mycobacterium, releasing the proton and causing a lethal disruption of the membrane. Although it has been shown that mutations causing significant loss of pyrazinamidase activity significantly contribute to pyrazinamide resistance, the mechanism of resistance is not completely understood.The pyrazinoic acid efflux rate may depend on multiple factors, including pyrazinamidase activity, intracellular pyrazinamidase concentration, and the efficiency of the efflux pump. Whilst the importance of the pyrazinoic acid efflux rate to the susceptibility to pyrazinamide is recognized, its quantitative effect remains unknown.Thirty-four M. tuberculosis clinical isolates and a Mycobacterium smegmatis strain (naturally resistant to PZA) were selected based on their susceptibility to pyrazinamide, as measured by Bactec 460TB and the Wayne method. For each isolate, the initial velocity at which pyrazinoic acid is released from the bacteria and the initial velocity at which pyrazinamide enters the bacteria were estimated.The data indicated that pyrazinoic acid efflux rates for pyrazinamide-susceptible M. tuberculosis strains fell within a specific range, and M. tuberculosis strains with a pyrazinoic acid efflux rate below this range appeared to be resistant. This finding contrasts with the high pyrazinoic acid efflux rate for M. smegmatis, which is innately resistant to pyrazinamide: its pyrazinoic acid efflux rate was found to be 900 fold higher than the average efflux rate for M. tuberculosis strains.No significant variability was observed in the pyrazinamide flux rate. The pyrazinoic acid efflux rate explained 61% of the variability in Bactec pyrazinamide susceptibility, 24% of Wayne activity, and 51% of the Bactec 460TB growth index. In contrast, pyrazinamidase activity accounted for only 27% of the Bactec pyrazinamide susceptibility. This finding suggests that mechanisms other than pncA mutations (reduction of pyrazinamidase activity) are also implicated in pyrazinamide resistance, and that pyrazinoic acid efflux rate acts as a better proxy for pyrazinamide resistance than the presence of pncA mutations. This is relevant to the design of molecular diagnostics for pyrazinamide susceptibility, which currently rely on pncA gene mutation detection.Pyrazinoic acid efflux rate in Mycobacterium tuberculosis is a better proxy of pyrazinamide resistanceMirko Zimic, Patricia Fuentes, Robert H. Gilman, Andrés H. Gutiérrez, Daniela Kirwan, Patricia Sheen10.1016/j.tube.2011.09.002Tuberculosis 92, 1 (2012)2011-10-17Tuberculosis2011-10-17921S1472-9792(12)X0002-7Drug Discovery and Resistance8491http://www.tuberculosisjournal.com/article/PIIS1472979211001648/abstract?rss=yesSummary: Multi Drug Resistant Tuberculosis Beijing strains exhibit different drug-resistance mutations (DRM) in different locations. By comparing DRM in Beijing reported from Tuberculosis endemic and epidemic locations, we propose that DRM selected in a population cannot tolerate biologically available drugs in different populations resulting in further evolution through novel DRM.Mycobacterium tuberculosis “Beijing” epidemics: A race against mutations?P. Bhatter, A. Chatterjee, N. Mistry10.1016/j.tube.2011.09.004Tuberculosis 92, 1 (2012)2011-10-19Tuberculosis2011-10-19921S1472-9792(12)X0002-7Drug Discovery and Resistance9294http://www.tuberculosisjournal.com/article/PIIS1472979211002204/abstract?rss=yesSummary: A link is hypothesized between inhibition of the retinoic acid receptor-related orphan receptor γ (RORγ) and treatment of Mycobacterium tuberculosis (Mtb) infection. An unexpected overlap was found between inhibitors of both Mtb H37Rv with RORγ in PubChem. Since RORγ is not present in Mtb, a commonality was reasoned to be cholesterol. Gemfibrozil is a RORγ inhibitor that was inactive against Mtb cells. Yet, gemfibrozil has been shown to inhibit Mtb growth in macrophages, supporting the hypothesis that RORγ inhibitors could show therapeutic benefit in Mtb infection.Is RORγ a therapeutic target for treating Mycobacterium tuberculosis infections?Paul W. Baures10.1016/j.tube.2011.11.009Tuberculosis 92, 1 (2012)2011-12-21Tuberculosis2011-12-21921S1472-9792(12)X0002-7Drug Discovery and Resistance9599http://www.tuberculosisjournal.com/article/PIIS1472979211001673/abstract?rss=yesSummary: Unusual drug accumulation is a common mechanism underlying serious drug-induced liver injury. Polymorphisms in three drug transporter genes (ABCB1, SLCO1B1 and ABCC2) may be risk markers for hepatitis induced by the unusual accumulation of anti-tuberculosis drugs (ATDs). We therefore investigated whether polymorphisms and haplotypes of these genes are associated with ATD-induced hepatitis by comparing the frequencies and distributions of single nucleotide polymorphisms and haplotypes of these three drug transporter genes among 67 patients with ATD-induced hepatitis and 159 patients tolerant to ATDs using a multivariate logistic regression analysis. We found that the frequencies of polymorphisms and haplotypes of ABCB1, SLCO1B1 and ABCC2 were similar in patients with ATD-induced hepatitis and ATD-tolerant controls. The present results suggest that these drug transporters do not play important roles in the pathogenesis of ATD-induced hepatitis in Korean patients.Polymorphisms in drug transporter genes (ABCB1, SLCO1B1 and ABCC2) and hepatitis induced by antituberculosis drugsSang-Hoon Kim, Sang-Heon Kim, Jae-Hyung Lee, Byoung-Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee10.1016/j.tube.2011.09.007Tuberculosis 92, 1 (2012)2011-12-19Tuberculosis2011-12-19921S1472-9792(12)X0002-7Host Genetics of Susceptibility100104http://www.tuberculosisjournal.com/article/PIIS1472979211001636/abstract?rss=yesSummary: The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two “subunit” type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each “vaccine” tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites.Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosisAjay Grover, JoLynn Troudt, Kimberly Arnett, Linda Izzo, Megan Lucas, Katie Strain, Christine McFarland, Yper Hall, David McMurray, Ann Williams, Karen Dobos, Angelo Izzo10.1016/j.tube.2011.09.003Tuberculosis 92, 1 (2012)2011-10-03Tuberculosis2011-10-03921S1472-9792(12)X0002-7Model Systems105111