Essential Gene Thymidylate Synthase Is Involved in Immune Modulation and Survival inside the Host.

A essential gene, ThyX (Rv2754c), plays a key role in intermediate metabolism and respiration by catalyzing the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate. ThyX is present in the complex and in a nonpathogenic strain of Mycobacteria. In this study, we identified a novel function of ThyX, an enzyme with immune-modulating properties.

Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade.

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy.

B cells promote granulomatous inflammation during chronic Mycobacterium tuberculosis infection in mice.

The current study reveals that in chronic TB, the B cell-deficient μMT strain, relative to wild-type (WT) C57BL/6 mice, displays in the lungs lower levels of inflammation that are associated with decreased CD4+ T cell proliferation, diminished Th1 response, and enhanced levels of interleukin (IL)-10. The latter result raises the possibility that B cells may restrict lung expression of IL-10 in chronic TB. These observations are recapitulated in WT mice depleted for B cells using anti-CD20 antibodies.

The PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response.

() is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. escapes from host macrophage through evasion or subversion of immune effector functions.

PGRS Domain of Rv0297 of Functions in A Calcium Dependent Manner.

, the pathogen causing tuberculosis, is a major threat to human health worldwide. Nearly 10% of genome encodes for a unique family of PE/PPE/PGRS proteins present exclusively in the genus Mycobacterium. The functions of most of these proteins are yet unexplored.

Teleological cooption of Mycobacterium tuberculosis PE/PPE proteins as porins: Role in molecular immigration and emigration.

Permeation through bacterial cells for exchange or uptake of biomolecules and ions invariably depend upon the existence of pore-forming proteins (porins) in their outer membrane. Mycobacterium tuberculosis (M. tb) harbours one of the most rigid cell envelopes across bacterial genera and is devoid of the classical porins for solute transport across the cell membrane.

PGRS Domain of Rv0297 of Is Involved in Modulation of Macrophage Functions to Favor Bacterial Persistence.

Rv0297-encoded PE_PGRS5 has been known to be expressed at the later stages of infection and in acidified phagosomes during transcriptome and proteomic studies. The possible role of Rv0297 in the modulation of phagosomal maturation and in providing protection against a microbicidal environment has been hypothesized. We show that Rv0297PGRS is involved in modulating the calcium homeostasis of macrophages followed by impedance of the phagolysosomal acidification process.

The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4.

The genome of , the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus and nowhere else in the living kingdom, with largely unexplored functions. We describe the functional significance of the PGRS domain of Rv0297, a member of this family. analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS).