Mycobacterium tuberculosis
Research Article | Therapeutics and PreventionThe Diversity Outbred Mouse Population Is an Improved Animal Model of Vaccination against Tuberculosis That Reflects Heterogeneity of ProtectionWe 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...
Research Article | Host-Microbe BiologyBazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing AutophagySince 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....
Commentary | Host-Microbe BiologymSphere of Influence: Combining Host and Pathogen Genetics To Disrupt Chronic InfectionsAndrew 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...
![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>](https://msphere.asm.org/sites/default/files/styles/thumbnail/public/externals/7b56615af4441ab7b2840e5d31309242.jpg?itok=kywyIsdP)
Research Article | Therapeutics and PreventionIdentification of 4-Amino-Thieno[2,3-d]Pyrimidines as QcrB Inhibitors in Mycobacterium tuberculosisThe 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...
Research Article | Therapeutics and PreventionTreatment of Virulent Mycobacterium tuberculosis and HIV Coinfected Macrophages with Gallium Nanoparticles Inhibits Pathogen Growth and Modulates Macrophage Cytokine ProductionGaNP 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-...
Commentary | Host-Microbe BiologymSphere of Influence: Clearing a Path for High-Resolution Visualization of Host-Pathogen Interactions In VivoShumin 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....
Research Article | Host-Microbe BiologyVitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against Mycobacterium tuberculosisTuberculosis (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...
Editor's Pick Research Article | Host-Microbe BiologyScreening Mycobacterium tuberculosis Secreted Proteins Identifies Mpt64 as a Eukaryotic Membrane-Binding Bacterial EffectorAdvances 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...
Research Article | Host-Microbe BiologySerum IgM Glycosylation Associated with Tuberculosis Infection in MiceWe demonstrate that M. tuberculosis infection influenced host protein glycosylation in a mouse model. The mechanism by which infection modifies glycans in serum proteins is not understood. Investigation of the regulation of such modifications by M. tuberculosis opens a new field that could lead to the discovery of novel biomarkers. Validation of such findings in human samples will reveal the clinical relevance of these...
Research Article | Molecular Biology and PhysiologyActivation of Bacterial Histidine Kinases: Insights into the Kinetics of the cis Autophosphorylation MechanismTwo-component systems consisting of an input-sensing histidine kinase (HK) and an output-generating response regulator (RR) are one of the key apparatuses utilized by bacteria for adapting to the extracellular milieu. HK autophosphorylation is shown to occur primarily in trans (intermolecular) and more recently shown to occur in cis (intramolecular). Although the catalysis of HK activation remains universal, the...