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Mycobacterium tuberculosis

  • Open Access
    Coexpression of MmpS5 and MmpL5 Contributes to Both Efflux Transporter MmpL5 Trimerization and Drug Resistance in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Research Article | Molecular Biology and Physiology
    Coexpression of MmpS5 and MmpL5 Contributes to Both Efflux Transporter MmpL5 Trimerization and Drug Resistance in Mycobacterium tuberculosis

    It has been reported that mycobacterial membrane protein large 5 (MmpL5), a resistance-nodulation-division (RND)-type inner membrane transporter in Mycobacterium tuberculosis (Mtb), is involved in the transport of antimycobacterial drugs. However, the functional roles of the membrane fusion protein mycobacterial membrane protein small 5 (MmpS5), organized as...

    Kentaro Yamamoto, Noboru Nakata, Tetsu Mukai, Ikuro Kawagishi, Manabu Ato
  • Open Access
    Analysis of Serial Multidrug-Resistant Tuberculosis Strains Causing Treatment Failure and Within-Host Evolution by Whole-Genome Sequencing
    Research Article | Molecular Biology and Physiology
    Analysis of Serial Multidrug-Resistant Tuberculosis Strains Causing Treatment Failure and Within-Host Evolution by Whole-Genome Sequencing

    Few studies have focused on the reasons for the low cure rate of multidrug-resistant tuberculosis in China and within-host evolution during treatment, which is of great significance for improving clinical treatment regimens. Acquired resistance events were common during the ineffective treatment, among which resistance to amikacin and high-level moxifloxacin were the most common.

    Xinchang Chen, Guiqing He, Siran Lin, Shiyong Wang, Feng Sun, Jiazhen Chen, Wenhong Zhang
  • Open Access
    The Diversity Outbred Mouse Population Is an Improved Animal Model of Vaccination against Tuberculosis That Reflects Heterogeneity of Protection
    Research Article | Therapeutics and Prevention
    The Diversity Outbred Mouse Population Is an Improved Animal Model of Vaccination against Tuberculosis That Reflects Heterogeneity of Protection

    We vaccinated the Diversity Outbred (DO) population of mice with BCG, the only vaccine currently used to protect against tuberculosis, and then challenged them with M. tuberculosis by aerosol. We found that the BCG-vaccinated DO mouse population exhibited a wide range of outcomes, in which outcomes in individual mice ranged from minimal respiratory or systemic disease...

    Sherry L. Kurtz, Amy P. Rossi, Gillian L. Beamer, Dan M. Gatti, Igor Kramnik, Karen L. Elkins
  • Open Access
    Bazedoxifene Suppresses Intracellular <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Growth by Enhancing Autophagy
    Research Article | Host-Microbe Biology
    Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

    Since current strategies for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have low efficacy and highly negative side effects, research on new treatments including novel drugs is essential for curing drug-resistant tuberculosis. Host-directed therapy (HDT) has become a promising idea to modulate host cell responses to enhance protective immunity against pathogens....

    Qi Ouyang, Kehong Zhang, Dachuan Lin, Carl G. Feng, Yi Cai, Xinchun Chen
  • Open Access
    mSphere of Influence: Combining Host and Pathogen Genetics To Disrupt Chronic Infections
    Commentary | Host-Microbe Biology
    mSphere of Influence: Combining Host and Pathogen Genetics To Disrupt Chronic Infections

    Andrew J. Olive works in the field of host responses to chronic infections. In this mSphere of Influence article, he reflects on how “Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing” (Y. J. Zhang, M. C. Reddy, T. R. Ioerger, A. C. Rothchild, et al., Cell 155:1296–1308, 2013, https://doi.org/10.1016/j.cell.2013.10.045) impacted his own work using...

    Andrew J. Olive
  • Open Access
    Identification of 4-Amino-Thieno[2,3-<em>d</em>]Pyrimidines as QcrB Inhibitors in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Research Article | Therapeutics and Prevention
    Identification of 4-Amino-Thieno[2,3-d]Pyrimidines as QcrB Inhibitors in Mycobacterium tuberculosis

    The global tuberculosis (TB) epidemic has been exacerbated by the rise in drug-resistant TB cases worldwide. To tackle this crisis, it is necessary to identify new vulnerable drug targets in Mycobacterium tuberculosis, the causative agent of TB, and develop compounds that can inhibit the bacterium through novel mechanisms of action. The QcrB subunit of the electron...

    Gregory A. Harrison, Anne E. Mayer Bridwell, Megh Singh, Keshav Jayaraman, Leslie A. Weiss, Rachel L. Kinsella, Janessa S. Aneke, Kelly Flentie, Miranda E. Schene, Margaret Gaggioli, Samantha D. Solomon, Scott A. Wildman, Marvin J. Meyers, Christina L. Stallings
  • Open Access
    Treatment of Virulent <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> and HIV Coinfected Macrophages with Gallium Nanoparticles Inhibits Pathogen Growth and Modulates Macrophage Cytokine Production
    Research Article | Therapeutics and Prevention
    Treatment of Virulent Mycobacterium tuberculosis and HIV Coinfected Macrophages with Gallium Nanoparticles Inhibits Pathogen Growth and Modulates Macrophage Cytokine Production

    GaNP interrupts iron-mediated enzymatic reactions, leading to growth inhibition of virulent HIV-M. tuberculosis coinfection in macrophages, and also modulates release of cytokines that may contribute to HIV-TB pathogenesis. Macrophage-targeting GaNP are a promising therapeutic approach to provide sustained antimicrobial activity against HIV-...

    Seoung-ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy
  • Open Access
    mSphere of Influence: Clearing a Path for High-Resolution Visualization of Host-Pathogen Interactions <em>In Vivo</em>
    Commentary | Host-Microbe Biology
    mSphere of Influence: Clearing a Path for High-Resolution Visualization of Host-Pathogen Interactions In Vivo

    Shumin Tan works in the field of Mycobacterium tuberculosis-host interactions. In this mSphere of Influence article, she reflects on how the paper “Single-cell phenotyping within transparent intact tissue through whole-body clearing” by B. Yang et al. (Cell 158:945–958, 2014, https://doi.org/10.1016/j.cell.2014.07....

    Shumin Tan
  • Open Access
    Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Research Article | Host-Microbe Biology
    Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against Mycobacterium tuberculosis

    Tuberculosis (TB) is the leading cause of death by a single infectious agent worldwide. One factor that contributes to the success of the microbe is the deficiency in immunomodulatory nutrients, such as vitamin A (retinol), which are prevalent in areas where TB is endemic. Clinical trials show that restoration of systemic retinol levels in active TB patients is ineffective in mitigating the disease; however, laboratory studies...

    Elliot W. Kim, Avelino De Leon, Zhichun Jiang, Roxana A. Radu, Adrian R. Martineau, Edward D. Chan, Xiyuan Bai, Wen-Lin Su, Dennis J. Montoya, Robert L. Modlin, Philip T. Liu
  • Open Access
    Screening <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Secreted Proteins Identifies Mpt64 as a Eukaryotic Membrane-Binding Bacterial Effector
    Editor's Pick Research Article | Host-Microbe Biology
    Screening Mycobacterium tuberculosis Secreted Proteins Identifies Mpt64 as a Eukaryotic Membrane-Binding Bacterial Effector

    Advances have been made to identify secreted proteins of Mycobacterium tuberculosis during animal infections. These data, combined with transposon screens identifying genes important for M. tuberculosis virulence, have generated a vast resource of potential...

    Chelsea E. Stamm, Breanna L. Pasko, Sujittra Chaisavaneeyakorn, Luis H. Franco, Vidhya R. Nair, Bethany A. Weigele, Neal M. Alto, Michael U. Shiloh

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