Tuberculosis Research and Epidemiology

Complete genomes reveal the full extent of Mycobacterium tuberculosis complex diversity across evolutionary scales

The paper uses long-read sequencing to generate complete genomes of Mycobacterium tuberculosis complex isolates, revealing increased genomic diversity and improved resolution in transmission analysis.

Loss of Ag85A disrupts plasma membrane domains and promotes free mycolic acid accumulation in mycobacteria.

This study shows that Ag85A is essential for plasma membrane domain organization in mycobacteria, leading to mycolic acid accumulation and altered cell envelope structure.

Granulysin antimicrobial activity promotes dormancy in Mycobacterium tuberculosis

The paper investigates how granulysin from immune cells induces dormancy in Mycobacterium tuberculosis, revealing an immune escape mechanism.

NK cell-macrophage interactions in granulomas correlate with limited tuberculosis pathology

The paper uses imaging mass cytometry to analyze granulomas in Mtb-infected non-human primates, finding that NK cell-macrophage interactions correlate with reduced tuberculosis pathology.

A Mycobacterium tuberculosis rare variable antigen vaccine reduces lung pathology without affecting bacterial burdens

A vaccine using rare variable antigens (RVMA) reduces lung pathology in mice without lowering bacterial loads during Mtb infection.

PE11 promotes intracellular persistence of Mycobacterium tuberculosis by inhibiting autophagy and lysosomal biogenesis by targeting the FLCN-lactate-TFEB signaling axis

This study identifies PE11 as a factor that promotes Mtb persistence by inhibiting autophagy and lysosomal biogenesis through the FLCN-lactate-TFEB signaling axis, with lactate shown to enhance bacterial clearance.

MDSC depletion during immunization with heat-killed Mycobacterium tuberculosis increases protection against BCG infection.

The paper shows that Mtb immunization protects against BCG infection despite inducing M-MDSC, and ATRA reduces M-MDSC to enhance immunity.

Disulfide bonds are required for cell division, cell envelope biogenesis and antibiotic resistance proteins in mycobacteria

The paper identifies cell envelope proteins in mycobacteria that require disulfide bonds for stability and shows that inhibiting the DsbA-VKOR pathway affects cell division and antibiotic resistance.

Mechanism of the Dual Action Self-Potentiating Antitubercular Drug Morphazinamide

This study identifies a dual mechanism of action for morphazinamide, a more potent pyrazinamide analog, showing it kills Mycobacterium tuberculosis through coenzyme A disruption and aldehyde release, which also bypasses resistance.

Integration of multi-modal measurements identifies critical mechanisms of tuberculosis drug action

This study introduces DECIPHAER, a tool that identifies critical mechanisms of tuberculosis drug action by integrating multi-modal data, revealing that respiration inhibition is more impactful than cell wall effects.

Protocol for Developing a Mouse Model of Post Primary Pulmonary Tuberculosis after Hematogenous Spread in Native Lungs and Lung Implants

This paper describes a mouse model of post-primary pulmonary tuberculosis that simulates hematogenous spread to the lungs and allows study of lung-specific TB mechanisms.

Human iPSC derived alveolar macrophages reveal macrophage subtype specific functions of itaconate in M. tuberculosis host defense

This study investigates itaconate's role in human macrophages, showing distinct effects in alveolar-like and M-CSF-derived macrophages during M. tuberculosis infection.

Distinct antibody-based signatures and functionality distinguish latent and active pediatric tuberculosis

The paper identifies distinct antibody-based signatures and functionalities in latent and active pediatric tuberculosis, highlighting differences in humoral immune responses that may inform diagnostic and therapeutic strategies.

Unpacking bedaquiline hetero-resistance: the importance of intermediate profiles for phenotypic drug-susceptibility testing

This paper shows that considering intermediate results in phenotypic drug susceptibility testing can detect bedaquiline heteroresistance at low frequencies, improving resistance determination.

RNA polymerase-mediated regulation of intrinsic antibiotic resistance and bacterial cell division

This study identifies a novel mechanism by which rifampin shortens TB treatment by inhibiting Mtb RNA polymerase, leading to cell division arrest and reduced antibiotic resistance.

Netupitant Exhibits Potent Activity on Mycobacterium tuberculosis Persisters

This study identifies netupitant as a compound that enhances anti-TB drug activity and eliminates Mtb persisters, showing potent bacteriostatic and tuberculocidal effects in combination with standard drugs.

Macrophage Cholesterol Homeostasis Underpins the role of Sertraline as an Adjunctive Agent in Tuberculosis Therapy.

This paper shows sertraline enhances macrophage bactericidal activity against Mtb by rewiring cholesterol metabolism and activating inflammasome pathways.

N-acetyl-transferases required for iron uptake and aminoglycoside resistance promote virulence lipid production in M. marinum

This study identifies N-acetyltransferases in M. marinum that link iron uptake, aminoglycoside resistance, and virulence lipid production, revealing their multifunctional roles in pathogenesis.

Early Antibody-Mediated Immunity to Tuberculosis in Mice Requires NLRP3

This study shows that antibodies against Mtb enhance immunity via NLRP3 inflammasome activation in mice, independent of Fc receptors, and this mechanism applies to polyclonal sera in rhesus macaques.

Increased vaccine efficacy against tuberculosis with a recombinant BCG overexpressing the STING agonist cyclic di AMP

This study evaluates a modified BCG vaccine overexpressing cyclic di-AMP, showing improved protection against TB in rhesus macaques.

MIP3α-RelMtb intranasal DNA vaccination induces reactive T-cell infiltration into the lungs in mice and macaques

This study shows that an intranasal DNA vaccine targeting RelMtb with MIP3α induces T-cell infiltration in the lungs of mice and macaques, enhancing immune responses against Mtb.

TREM2+ macrophages accumulate in alveoli of human pulmonary tuberculosis providing a permissive niche for bacterial growth

This study identifies TREM2+ lipid-laden macrophages in alveolar TB pneumonia that support Mtb survival, contrasting with granulomas, and shows pharmacological reversal of this immunometabolic state.

Increased proportion of growth-arrested bacilli in acidic pH adaptation promotes Mycobacterium tuberculosis treatment survival

This study shows that Mycobacterium tuberculosis adapts to acidic conditions by increasing growth-arrested cells, which enhance drug tolerance and survival.

Sertraline enhances bacterial control by improving the pharmacodynamic -pharmacokinetic properties of frontline TB drugs

This study shows sertraline improves bacterial control in TB models by enhancing the pharmacodynamic-pharmacokinetic properties of TB drugs without altering their distribution or clearance.

Dissecting the effect of single- and co- infection of TB and COVID-19 pathogens on the sputum microbiome

This study investigates how TB and COVID-19 co-infection affects the sputum microbiome, finding altered bacterial abundance and functional pathways that may impact treatment outcomes.

Effects of CwlM, a peptidoglycan synthesis regulator, on beta-lactam resistance and host-pathogen interactions

This study investigates the role of CwlM in beta-lactam resistance and intracellular survival in Mycobacterium smegmatis, finding it promotes resistance and supports survival in macrophages without PG-hydrolytic activity.

A periplasmic protein complex supports arabinofuranosyltransferase activity and mediates intrinsic drug resistance in Mycobacterium tuberculosis

This study identifies a periplasmic protein complex in Mtb that supports arabinofuranosyltransferase activity and contributes to intrinsic drug resistance.

Beating the gold standard: A review of Mycobacterium tuberculosis lysis using bead beating and the need for standardization.

The paper reviews bead beating methods for Mycobacterium tuberculosis lysis, identifies protocol variability, and highlights the need for standardization to improve reproducibility.

Lipid-mediated GPR32 signaling reprograms macrophage metabolism to impair anti-tuberculous immunity

The paper identifies RvD5-GPR32 signaling as a mechanism by which TB-PE reprograms macrophage metabolism to impair anti-tuberculous immunity.

A mouse model of TB-associated lung fibrosis reveals persistent inflammatory macrophage populations during treatment

This study uses a mouse model of TB infection to investigate fibrosis mechanisms, finding persistent inflammatory macrophages and elevated matrix remodeling enzymes during treatment.