The candidate vaccine derived from H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice.

Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection.

Hippo pathway: Regulation, deregulation and potential therapeutic targets in cancer.

Hippo pathway is a master regulator of development, cell proliferation, stem cell function, tissue regeneration, homeostasis, and organ size control. Hippo pathway relays signals from different extracellular and intracellular events to regulate cell behavior and functions. Hippo pathway is conserved from Protista to eukaryotes.

An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.

BCG is widely used as a vaccine against tuberculosis due to (Mtb), which kills millions of people each year. BCG variably protects children, but not adults against tuberculosis. BCG evades phagosome maturation, autophagy, and reduces MHC-II expression of antigen-presenting cells (APCs) affecting T-cell activation.

Reactive oxygen species and cancer: A complex interaction.

Elevated levels of Reactive Oxygen Species (ROS), increased antioxidant ability and the maintenance of redox homeostasis can cumulatively contribute to tumor progression and metastasis. The sources and the role of ROS in a heterogeneous tumor microenvironment can vary at different stages of tumor: initiation, development, and progression, thus making it a complex subject. In this review, we have summarized the sources of ROS generation in cancer cells, its role in the tumor microenvironment, the possible functions of ROS and its important scavenger systems in tumor progression with special emphasis on solid tumors.

Inactivation of the organic hydroperoxide stress resistance regulator OhrR enhances resistance to oxidative stress and isoniazid in Mycobacterium smegmatis.

The organic hydroperoxide stress resistance regulator (OhrR) is a MarR type of transcriptional regulator that primarily regulates the expression of organic hydroperoxide reductase (Ohr) in bacteria. In mycobacteria, the genes encoding these proteins exist in only a few species, which include the fast-growing organism Mycobacterium smegmatis. To delineate the roles of Ohr and OhrR in defense against oxidative stress in M.

Differential expression of miRNAs by macrophages infected with virulent and avirulent Mycobacterium tuberculosis.

MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate a wide range of biological processes that include cellular differentiation, development, immunity and apoptosis. There is a growing body of evidences that bacteria modulate immune responses by altering the expression of host miRNAs. Since macrophages are immune cells associated with innate and adaptive immunity, we investigated whether Mycobacterium tuberculosis infection affects miRNAs of macrophages.

A serine/threonine phosphatase encoded by MG_207 of Mycoplasma genitalium is critical for its virulence.

Background: Bacterial signal transduction systems like two component system (TCS) and Serine/Threonine kinase (STK) and Serine/Threonine phosphatase (STP) play important roles in the virulence and pathogenesis of bacterial pathogens. Mycoplasma genitalium, a mollicute that causes the urogenital diseases urethritis and cervicitis in men and women, respectively, is a pathogen which lacks TCS but possesses STK/STP. In this study, we investigated the biochemical and virulence properties of an STP protein encoded by the gene MG_207 of this species.

The fbpA/sapM double knock out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death due to bacterial infections in mankind, and BCG, an attenuated strain of Mycobacterium bovis, is an approved vaccine. BCG sequesters in immature phagosomes of antigen presenting cells (APCs), which do not fuse with lysosomes, leading to decreased antigen processing and reduced Th1 responses. However, an Mtb derived ΔfbpA attenuated mutant underwent limited phagosome maturation, enhanced immunogenicity and was as effective as BCG in protecting mice against TB.

Methionine sulfoxide reductase A (MsrA) deficient Mycoplasma genitalium shows decreased interactions with host cells.

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M.

OsmC proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis protect against organic hydroperoxide stress.

Bacterial antioxidants play a critical role in the detoxification of endogenously and host derived oxidative radicals during host-pathogen interactions. Recently, the osmotically induced bacterial protein C (OsmC) is included in the antioxidant category of enzymes as it shows structural and functional relationships with organic hydroperoxide reductase (Ohr) enzyme. A copy of the gene encoding OsmC is conserved across mycobacterial species, including Mycobacterium tuberculosis (Rv2923c) and Mycobacterium smegmatis (MSMEG2421), but its role in protecting these species against oxidative stress is unknown.

Biochemical and physiological characterization of the GTP-binding protein Obg of Mycobacterium tuberculosis.

Background: Obg is a highly conserved GTP-binding protein that has homologues in bacteria, archaea and eukaryotes. In bacteria, Obg proteins are essential for growth, and they participate in spore formation, stress adaptation, ribosome assembly and chromosomal partitioning. This study was undertaken to investigate the biochemical and physiological characteristics of Obg in Mycobacterium tuberculosis, which causes tuberculosis in humans.

Methionine sulfoxide reductase B (MsrB) of Mycobacterium smegmatis plays a limited role in resisting oxidative stress.

Pathogenic mycobacteria including Mycobacterium tuberculosis resists phagocyte generated reactive oxygen intermediates (ROI) and this constitutes an important virulence mechanism. We have previously reported, using Mycobacterium smegmatis as a model to identify the bacterial components that resist intracellular ROI, that an antioxidant methionine sulfoxide reductase A (MsrA) plays a critical role in this process. In this study, we report the role of methionine sulfoxide reductase B (MsrB) in resistance to ROI by constructing a msrB mutant (MSDeltamsrB) and MsrA/B double mutant (MSDeltamsrA/B) strains of M.

The Mycoplasma genitalium MG_454 gene product resists killing by organic hydroperoxides.

Mycoplasma genitalium is the smallest self-replicating organism and a successful human pathogen associated with a range of genitourinary maladies. As a consequence of its restricted genome size, genes that are highly conserved in other bacteria are absent in M. genitalium.

Methionine sulfoxide reductases and virulence of bacterial pathogens.

Oxidation of methionine (Met) residues in proteins by reactive oxygen species and reactive nitrogen intermediates results in altered protein structures, which subsequently affect their functions. Oxidized Met (Met-O) residues are reduced to Met by the methionine sulfoxide reductase (Msr) system, which includes mainly MsrA and MsrB. MsrA and MsrB show no sequence and structural identity with each other but both reduce methionine sulfoxides.