Mycobacterium tuberculosis
Research Article | Molecular Biology and PhysiologyA CRISPR-Assisted Nonhomologous End-Joining Strategy for Efficient Genome Editing in Mycobacterium tuberculosisThe global health impact of M. tuberculosis necessitates the development of new genetic tools for its manipulation, to facilitate the identification and characterization of novel drug targets and vaccine candidates. Clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein (Cas) genome editing has proven to be a powerful genetic tool...
Observation | Host-Microbe BiologyIntracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann CellsLeprosy remains a major problem in the world today, particularly affecting the poorest and most disadvantaged sections of society in the least developed countries of the world. The long-term aim of research is to develop new treatments and vaccines, and these aims are currently hampered by our inability to grow the pathogen in axenic culture. In this study, we probed the metabolism of...
Research Article | Host-Microbe BiologyFunctionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross MiceThe variable outcome of Mycobacterium tuberculosis infection observed in natural populations is difficult to model in genetically homogeneous small-animal models. The newly developed Collaborative Cross (CC) represents a reproducible panel of genetically diverse mice that display a broad range of phenotypic responses to infection. We explored the genetic basis of this...
Research Article | Therapeutics and PreventionTranscriptomic Signatures Predict Regulators of Drug Synergy and Clinical Regimen Efficacy against TuberculosisMultidrug combination therapy is an important strategy for treating tuberculosis, the world’s deadliest bacterial infection. Long treatment durations and growing rates of drug resistance have created an urgent need for new approaches to prioritize effective drug regimens. Hence, we developed a computational model called INDIGO-MTB that identifies synergistic drug regimens from an immense set of possible drug combinations using the...
Research Article | Host-Microbe BiologyCD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species ProductionTuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and β-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB...
Research Article | Host-Microbe BiologyCommon Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug EfficacyTB control is limited in part by the length of antibiotic treatment needed to prevent recurrent disease. To probe mechanisms underlying survival under antibiotic pressure, we performed a genetic screen for M. tuberculosis mutants with altered susceptibility to treatment using the mouse model of TB. We identified multiple genes involved in a range of functions which...
Research Article | Molecular Biology and PhysiologymRNA Degradation Rates Are Coupled to Metabolic Status in Mycobacterium smegmatisThe logistics of tuberculosis therapy are difficult, requiring multiple drugs for many months. Mycobacterium tuberculosis survives in part by entering nongrowing states in which it is metabolically less active and thus less susceptible to antibiotics. Basic knowledge on how M. tuberculosis survives...
Research Article | Host-Microbe BiologyTwo Accessory Proteins Govern MmpL3 Mycolic Acid Transport in MycobacteriaThe cell envelope of Mycobacterium tuberculosis, the bacterium that causes the disease tuberculosis, is a complex structure composed of abundant lipids and glycolipids, including the signature lipid of these bacteria, mycolic acids. In this study, we identified two new components of the transport machinery that constructs this complex cell wall. These two accessory...
Research Article | Molecular Biology and PhysiologyMycofactocin Is Associated with Ethanol Metabolism in MycobacteriaTuberculosis is caused by Mycobacterium tuberculosis, and the increasing emergence of multidrug-resistant strains renders current treatment options ineffective. Although new antimycobacterial drugs are urgently required, their successful development often relies on complete understanding of the metabolic pathways—e.g., cholesterol assimilation—that are critical for...
Editor's Pick Research Article | Therapeutics and PreventionBacterial Genome-Wide Association Identifies Novel Factors That Contribute to Ethionamide and Prothionamide Susceptibility in Mycobacterium tuberculosisPhenotypic antibiotic susceptibility testing in Mycobacterium tuberculosis is slow and cumbersome. Rapid molecular diagnostics promise to help guide therapy, but such assays rely on complete knowledge of the molecular determinants of altered antibiotic susceptibility. Recent genomic studies of antibiotic-resistant M. tuberculosis have identified several...