Tuberculosis Research and Epidemiology

A FRET-based high-throughput screening assay for the discovery of Mycobacterium tuberculosis DNA ADP-ribosylglycohydrolase DarG inhibitors

This paper develops a FRET-based high-throughput screening assay to identify DarG inhibitors in M. tuberculosis and identifies pranlukast as a selective inhibitor.

Airflow Constraints Limit Natural Airborne Transmission of Tuberculosis

This study shows that airflow constraints can suppress tuberculosis transmission in guinea pigs, even under conditions that would otherwise allow transmission.

In host mutational adaptation of Mycobacterium tuberculosis complex strains

The paper analyzes within-host genetic diversity of Mycobacterium tuberculosis complex strains to identify mutations associated with drug resistance and pathogenesis.

Single-Cell Immune Profiling Reveals Non-classical Monocyte-Driven Immunodepression in Tuberculosis Treatment Non-Responders

The paper identifies non-classical monocyte-driven immunodepression in TB treatment non-responders using single-cell RNA sequencing.

Infection with Mycobacterium tuberculosis orchestrates the PRMT5-dependent methylation of NCOA4 to govern host ferroptosis

This study identifies PRMT5-dependent methylation of NCOA4 as a mechanism by which Mtb induces ferroptosis in host macrophages to enhance its survival and dissemination.

Variability in intrinsic drug tolerance in Mycobacterium tuberculosis corresponds with phylogenetic lineage

The paper measures drug tolerance in Mycobacterium tuberculosis lineages and finds higher tolerance in L3 and L4 strains, with heritable patterns and enrichment of mutations in specific metabolic pathways.

Mouse Models Uniformly Featuring Human-like Lesions Harboring Drug-tolerant Mycobacterium tuberculosis

The paper develops two mouse models that consistently produce human-like hypoxic necrotic lesions with drug-tolerant Mycobacterium tuberculosis.

A multicenter spatial transcriptomics atlas of human tuberculosis and non-tuberculous mycobacterial disease

This study creates a spatial transcriptomics atlas of human tuberculosis and non-tuberculous mycobacterial granulomas, identifying distinct niches and immune signatures.

Systems-level characterization of EGFR kinase inhibitors reveals heterogeneous effects on Mtb-macrophage interactions

This study examines the effects of EGFR kinase inhibitors on Mtb-macrophage interactions, finding heterogeneous outcomes and both direct and host-dependent mechanisms of action.

Culture filtrate selectively promotes Mycobacterium tuberculosis growth from extremely low density inocula: implications for quantifying differentially culturable phenotypes

This study shows that culture filtrate selectively enhances Mycobacterium tuberculosis growth from low inoculum densities, but its effect diminishes at higher densities, suggesting limitations in current culturing methods.

Deciphering the transcriptomic landscape of pyrazinamide resistance in Mycobacterium tuberculosis

This study compares transcriptomic responses of a pyrazinamide-resistant Mycobacterium tuberculosis clinical strain and a drug-susceptible strain, identifying mutation-driven gene expression changes and cross-resistance mechanisms.

Molecular mechanism of the key dormancy regulator DosR-dependent transcription activation in Mycobacterium tuberculosis

This study determines the cryo-EM structure of the DosR-dependent transcriptional activation complex in Mtb and identifies its molecular mechanism for dormancy regulation.

Cholesterol-activated VapC12 toxin modulates growth and drug susceptibility in Mycobacterium tuberculosis

This study identifies a cholesterol-binding motif in the VapC12 toxin of M. tuberculosis and shows that cholesterol activates the toxin, reducing bacterial growth and antibiotic susceptibility.

BCG Vaccination at Birth Shapes the TCR Usage and Functional Profile of MR1T Cells at 9 Weeks of Age

This study examines how BCG vaccination at birth affects MR1T cell TCR usage and function in infants, finding increased type I interferon response and a TCR cluster enriched in vaccinated infants.

Shared and distinct responses of human and murine alveolar macrophages and monocyte-derived macrophages to Mycobacterium tuberculosis

This study compares human and murine macrophage responses to Mtb infection, identifying shared and distinct immune pathways and cytokine expression patterns between alveolar and monocyte-derived macrophages.

Methionine modulates the metabolic-epigenetic axis as immunotherapeutic in tuberculosis

This study shows methionine supplementation enhances pro-inflammatory responses and mycobacterial clearance in tuberculosis by modulating host metabolism and epigenetic pathways.

Rapidly and reproducibly building a comprehensive catalogueof resistance-associated variants for M. tuberculosis

This paper develops an automated method to build a comprehensive catalogue of resistance-associated variants for M. tuberculosis, achieving comparable performance to existing catalogues without expert rules.

Evolution of Mycobacterium tuberculosis transcription regulation is associated with increased transmission and drug resistance

The paper identifies variants in Mycobacterium tuberculosis associated with decreased virulence gene expression and increased transmissibility, particularly in drug-resistant strains.

Sterilizing activity of spectinamide MBX-4888A when replacing linezolid in the Nix-TB regimen in the relapsing BALB/c mouse model of tuberculosis

This study evaluates replacing linezolid with spectinamide MBX-4888A in the Nix-TB regimen for tuberculosis in a mouse model, showing potential for reduced adverse effects.

Pyrazinamide kills Mycobacterium tuberculosis via pH-driven weak-acid permeation and cytosolic acidification

This study investigates the mechanism of action of pyrazinamide (PZA) in Mycobacterium tuberculosis, showing it kills bacteria by acidifying cytosol via pH-driven weak-acid permeation, independent of PanD and pantothenate levels.

Genome-wide screen in Mycobacterium tuberculosis infected macrophages reveals innate regulation of antibacterial mediators by IRF2

The paper identifies IRF2 as a regulator of antibacterial responses in Mtb-infected macrophages through a genome-wide CRISPR screen, showing its inhibitory role in macrophage activation.

Validating Conditionally Essential Targets: Discovery of the First Orally Effective Biotin Inhibitor against MycobacteriumTuberculosis

The paper develops an orally effective biotin inhibitor, C48, against Mycobacterium tuberculosis, demonstrating in vivo efficacy in a low-biotin mouse model.

Rapid Screening and Validation of Intracellularly Active Antimycobacterial Compounds with Efficacy in Cellular and Murine Tuberculosis Models

This paper validates a THP-1 macrophage model with Mycobacterium marinum for rapid screening of intracellular antimycobacterial compounds, identifying phenothiazines as effective adjuncts to TB therapy.

Direct nanopore sequencing of M. tuberculosis on sputa and rescue of suboptimal results to enhance transmission surveillance

This study applies direct nanopore sequencing to sputum samples to accelerate MTB transmission surveillance, achieving epidemiologically useful results in half the samples analyzed.

Thienopyrimidine amide analogs target MmpL3 in Mycobacterium tuberculosis

The paper identifies thienopyrimidine amides as MmpL3 inhibitors in M. tuberculosis, showing loss of potency in MmpL3 mutants and cell wall stress responses.

In-silico evidence of non-operonic fusion transcripts in Mycobacterium tuberculosis: algorithm optimization and signatures of genome plasticity.

The paper identifies non-operonic fusion transcripts in Mycobacterium tuberculosis clinical isolates using optimized computational methods and shows evidence of genome plasticity through intragenomic recombination.

The C3HeB/FeJ Kramnik mouse as a model to investigate the efficacy of therapeutic tuberculosis interventions

This study evaluates the C3HeB/FeJ Kramnik mouse model for TB research by testing a novel Pheroid(R) formulation and highlights limitations in macrophage pathology and B-cell activity.

Nitrate-responsive Mycobacterial Intracytoplasmic Membranes dampen Inflammation during Mycobacterium tuberculosis Infection

This study identifies nitrate-induced intracytoplasmic membranes in Mycobacterium tuberculosis that help dampen inflammation during infection.

Mycobacterium tuberculosis Genes Needed for Intra-alveolar Resuscitation After Airborne Transmission

The paper identifies genes in Mycobacterium tuberculosis essential for intra-alveolar survival after airborne transmission, revealing stage-specific roles in transmission.

Targeting Mycobacterial Transpeptidases: Evaluating the Roles of Ldt and PBP Inhibition in Suppressing Mycobacterium smegmatis

This study evaluates the roles of Ldt and PBP inhibition in suppressing Mycobacterium smegmatis using beta-lactams and LdtMt2 inhibitors, finding stronger growth suppression with Ldt inhibition.