Tuberculosis Research and Epidemiology

The Dictyostelium discoideum - Mycobacterium marinum infection model, a powerful high throughput screening platform for anti-infective compounds

This paper introduces a high-throughput phenotypic host-pathogen assay using Dictyostelium discoideum and Mycobacterium marinum to screen anti-infective compounds, demonstrating its ability to differentiate between antibiotics and anti-infectives.

Loss of the PPE71-esxX-esxY-PPE38 locus drives adaptive transcriptional responses and hypervirulence of Mycobacterium tuberculosis Lineage 2

This study shows that loss of the PPE71-38 locus in Mycobacterium tuberculosis Lineage 2 increases stress response gene expression and triglyceride levels, contributing to hypervirulence.

Disruption of riboflavin biosynthesis in mycobacteria establishes 5-amino-6-D-ribitylaminouracil (5-A-RU) as key precursor of MAIT cell agonists

Deleting early riboflavin genes (ribA2 in both species, ribG in M. smegmatis) sharply reduced MAIT cell activation, while ribH deletion raised recognition of M. tuberculosis only.

Phosphoglucomutase A mediated regulation of carbon flux is essential for antibiotic and disease persistence in Mycobacterium tuberculosis

This study shows that phosphoglucomutase A (pgmA) is essential for Mycobacterium tuberculosis survival under nutrient-limiting conditions and disease persistence.

Mechanistic insights into the allosteric regulation of cell wall hydrolase RipA in Mycobacterium tuberculosis.

This study investigates the regulatory mechanism of RipA, a cell wall hydrolase in Mtb, through structural and functional analysis of the SteAB system.

Dexamethasone impairs glycolysis but improves mycobacterial killing in primary human macrophages

This study shows dexamethasone reduces glycolysis in human macrophages but enhances mycobacterial killing, suggesting a potential therapeutic benefit in tuberculosis.

Structural and functional analysis of the Mycobacterium tuberculosis MmpS5L5 efflux pump presages a pathway to increased bedaquiline resistance

This study determines the cryo-EM structure of the MmpS5L5 efflux pump in Mycobacterium tuberculosis and identifies mutations that enhance bedaquiline efflux, suggesting new resistance mechanisms.

Mycobacterial Metallophosphatase MmpE Acts as a Nucleomodulin to Regulate Host Gene Expression and Promote Intracellular Survival

This study identifies MmpE as a nucleomodulin in Mycobacterium tuberculosis that inhibits host inflammatory gene expression and promotes intracellular survival by targeting the VDR promoter and regulating the PI3K-Akt-mTOR pathway.

Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model

The paper investigates TB relapse in a macaque model, finding that complete sterilization protects against relapse but PET CT cannot predict it, and that Mtb dissemination originates from both lung and lymph nodes.

Feature selection and aggregation for antibiotic resistance GWAS in Mycobacterium tuberculosis: a comparative study.

This study compares feature selection methods for GWAS of antibiotic resistance in Mycobacterium tuberculosis, finding that ABESS outperforms others in selecting relevant mutations.

An improved catalogue for whole-genome sequencing prediction of bedaquiline resistance in M. tuberculosis using a reproduciblealgorithmic approach.

The paper develops an automated method to predict bedaquiline resistance in M. tuberculosis using a reproducible algorithmic approach, achieving high sensitivity and specificity in variant classification.

Verification of emerging genomic mutations in Mycobacterium tuberculosis allows transmission chains to be distinguished in an epidemiological typing cluster extending over thirty years.

The paper identifies emerging SNPs in Mycobacterium tuberculosis isolates to distinguish transmission chains in a long-term epidemiological cluster.

APOE Protects Against Severe Infection with Mycobacterium tuberculosis by Restraining Production of Neutrophil Extracellular Traps

This study shows that APOE protects against severe tuberculosis by limiting neutrophil extracellular trap formation, which exacerbates infection in Apoe-/- mice.

Exploring Mycobacterium tuberculosis rRNA Transcriptomic Signatures asResponse to Anti-TB Treatment in Whole Blood RNA-seq Data

The paper analyzes whole-blood RNA-seq data from TB patients to identify rRNA transcriptomic signatures that change during anti-TB treatment, suggesting potential biomarkers for monitoring treatment response.

Spatially-distinct programming of macrophage diversity within the granulomas of Mycobacterium tuberculosis infected nonhuman primates

The paper profiles macrophage diversity in TB granulomas using single-cell RNA sequencing and immunofluorescence in nonhuman primates, identifying distinct subsets and their roles in Mtb infection.

Mycobacterium tuberculosis effector protein PE5 hijacks the host CRL2 ubiquitin ligase complex

This paper identifies PE5, a Mycobacterium tuberculosis effector protein, as interacting with the host CRL2 ubiquitin ligase complex, modulating its activity without being ubiquitinated itself.

Uncovering asparagine utilization pathway, a critical requirement for mycobacterial pH-driven adaptation at the host-pathogen crossroads

The paper identifies PhoP's role in regulating asparagine utilization in M. tuberculosis under acidic conditions, showing its importance for bacterial survival in host phagosomes.

CD4+ T cells recruit, then engage macrophages in cognate interactions to clear Mycobacterium tuberculosis from the lungs.

This study shows CD4+ T cells recruit macrophages to clear Mtb by MHCII-mediated cognate interactions, not IFN-{gamma}, promoting glycolysis in macrophages for bacterial control.

Differential control of mycobacteria among COVID-19 patients is associated with CD28+ CD8+ T cells

The paper examines how CD28+ CD8+ T cells in COVID-19 patients influence mycobacterial growth inhibition.

The mycomembrane differentially and heterogeneously restricts antibiotic permeation

This paper shows that the mycomembrane of Mycobacterium tuberculosis and M. smegmatis differentially and heterogeneously restricts antibiotic permeation using the PAC-MAN method.

The kinetics of bedaquiline diffusion in tuberculous cavities opens a window for emergence of resistance.

Rabbit lesion microdissection and pharmacokinetic modeling show bedaquiline takes months to reach deep caseum and years to clear, while TBAJ-587 and TBAJ-876 shorten these windows.

Confirmation of HLA-II associations with TB susceptibility in admixed African samples

This study confirms an association between HLA-II region variants and TB susceptibility in admixed South African samples using the LAAA model.

Integrative transcriptome-based drug repurposing in tuberculosis

This study identifies 64 FDA-approved drugs as potential host-directed therapeutics for tuberculosis using an integrative transcriptome-based approach combining multiple gene expression signatures and connectivity scoring methods.

Rankings of tuberculosis antibiotic treatment regimens are sensitive to spatial scale, detection limit, and initial host bacterial burden

The paper simulates TB antibiotic regimens in a computational model to show rankings are influenced by spatial scale, detection limit, and initial bacterial burden.

Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction.

This study identifies protective antibodies against Mycobacterium tuberculosis and shows that their Fc-effector function and Fab domains collaborate to restrict infection through immune cell reorganization.

Dinucleotide codon mutations as a marker of diversifying selection in M. tuberculosis

The paper identifies dinucleotide substitutions in M. tuberculosis as markers of diversifying selection, revealing their role in drug resistance and virulence evolution.

Lung epithelial progenitor-mediated release of TGF-β regulates induction and persistence of lung CD8+ TRM cells following mucosal BCG vaccination

This study shows that mucosal BCG vaccination induces lung CD8+ TRM cells via TGF-β activation by airway epithelial progenitors, linking tissue repair to immune memory.

Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis

This study shows that cholesterol metabolism and potassium homeostasis are interconnected in Mycobacterium tuberculosis, with cholesterol modulating potassium transport and affecting bacterial growth.

Genetic requirements of Mycobacterium tuberculosis for survival under pathogen-specific immunity

This study identifies Mtb genes essential for survival in vaccinated and previously infected hosts using TnSeq, revealing differences in genetic requirements across immunization strategies.

Evaluation of the role of whiB6 and kdpDE in the dominant multidrug resistant clone Mycobacterium tuberculosis B0/W148

This study investigates two mutations in M. tuberculosis B0/W148 clone, finding they do not impair growth or virulence but alter transcriptional profiles.