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Related Articles from SNS
Inorganic sulfate transport by the Mycobacterium tuberculosis PE22/PPE36 complex
Mycobacterium tuberculosis (Mtb) encodes two multigene families with 169 members that are exclusive to mycobacteria, the pe and ppe genes. These genes have unusual sequences including low-complexity repeat regions, but their functions and whether they share a common function have long been unclear. Recently, several members of the pe/ppe family were shown to transport nutrients across the outer Mtb membrane, a role for which no other proteins have yet been identified.
Replicate-anchored calibration of within-host single nucleotide variant detection in Mycobacterium tuberculosis whole genome sequencing
Intra-host genetic heterogeneity in Mycobacterium tuberculosis is biologically and clinically informative, but its detection from short read whole genome sequencing depends on thresholds over read depth (DP), alternate allele support (AD), and minor allele frequency (MAF) that are rarely empirically anchored. We developed a biological replicate-anchored, lexicographic calibration framework for per-specimen intra-host single nucleotide variant (iSNV) detection. Within-patient replicate sputum...
Clinical isolates of Mycobacterium avium complex reveal an M. intracellulare-associated IL-17/neutrophilic pulmonary immune program in a murine disease model
Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly understood. Here, we established a panel of MAC clinical isolates exhibiting...
Galectin-3 recruitment at the Mycobacterium tuberculosis-containing phagosome is critical in macrophage but dispensable in epithelial cells
Mycobacterium tuberculosis (Mtb) virulence relies in part on its ability to induce phagosomal membrane rupture, enabling bacterial access to the host cell cytosol. This process is largely mediated by the ESX{middle dot}1 secretion system, which is present in Mtb but absent from the vaccine strain BCG. Galectin{middle dot}3 (Gal3), a {beta}{middle dot}galactoside{middle dot}binding lectin, is recruited to damaged endomembranes and functions as a cytosolic sensor of membrane disruption.
Modulation of Ferroptosis During Early Mycobacterium tuberculosis Infection Contributes to Beijing Lineage Strain SA161 Virulence
Although spread of internalized Mtb from the initial infected alveolar macrophages (AMs) is a crucial determinant of infection outcomes, the role of cell death in facilitating this spread, and how it is regulated by Mtb remains poorly understood. Ferroptosis, a lipid peroxidation-mediated form of necrotic cell death, contributes to pathology during later stages of infection. However, the role of ferroptosis in early AM cell death remains inadequately defined, and its induction during...
Researchers discover how to turn one germ's drug resistance into an Achilles' heel
Researchers discover how to turn one germ's drug resistance into an Achilles' heel Lisa Lock Scientific Editor Andrew Zinin Lead Editor Decades of reliance on the antibiotic rifampicin have fueled the rise of drug-resistant Mycobacterium tuberculosis (Mtb). But as the bacterium mutates to protect itself from the drug, it also creates new weak points that other therapies could exploit. Now, a new study published in Nature Microbiology shows that the most common rifampicin-resistance mutation...
Modeling development of tertiary lymphoid structures in pulmonary tuberculosis by 3D profiling and trajectory analysis
Tertiary lymphoid structures (TLSs) are sites of immune organization in peripheral tissues that arise from chronic inflammation. They play important roles in infection control and cancer but the mechanisms controlling their formation remain only partly understood. Here, we combine high-plex imaging, serial-section 3D reconstruction, and optimal transport trajectory modeling to reconstruct TLSs in human lungs infected with Mycobacterium tuberculosis.
Minimal effective dose of telacebec administered orally in a murine model of leprosy
Leprosy treatment requires prolonged therapy with challenging patient follow-up. New regimens are needed to simplify current treatments. A recent clinical trial evaluating bedaquiline has shown promising results; however, to prevent the emergence of drug resistance, additional therapeutic options are required.