BCG's role in strengthening immune responses: Implications for tuberculosis and comorbid diseases.

The BCG vaccine represents a significant milestone in the prevention of tuberculosis (TB), particularly in children. Researchers have been developing recombinant BCG (rBCG) variants that can trigger lasting memory responses, thereby enhancing protection against TB in adults. The breakdown of immune surveillance is a key link between TB and other communicable and non-communicable diseases.

Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1.

Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease-related deaths worldwide. It uses ESX-1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis.

Expression of a unique DNA MTase Rv1509 in alters the gene expression pattern and enhances virulence.

() genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using comparative genome analysis, we identified one of the genes, Rv1509, as a signature protein exclusively present in .

Rv2231c, a unique histidinol phosphate aminotransferase from Mycobacterium tuberculosis, supports virulence by inhibiting host-directed defense.

Nitrogen metabolism of M. tuberculosis is critical for its survival in infected host cells. M.

Activation of the lysosomal damage response and selective autophagy: the coordinated actions of galectins, TRIM proteins, and CGAS-STING1 in providing immunity against .

Autophagy is a crucial immune defense mechanism that controls the survival and pathogenesis of by maintaining cell physiology during stress and pathogen attack. The E3-Ub ligases (PRKN, SMURF1, and NEDD4) and autophagy receptors (SQSTM1, TAX1BP1, CALCOCO2, OPTN, and NBR1) play key roles in this process. Galectins (LGALSs), which bind to sugars and are involved in identifying damaged cell membranes caused by intracellular pathogens such as , are essential.

Are all VapC toxins of endowed with enigmatic RNase activity?

() employs an extensive network of more than 90 toxin-antitoxin systems, and among them, VapC toxins are the most abundant. While most VapCs function as classical RNases with toxic effects, a significant number of them do not exhibit toxicity. However, these non-toxic VapCs may retain specific RNA binding abilities as seen in case of VapC16, leading to ribosome stalling at specific codons and reprofiling 's proteome to aid in the bacterium's survival under different stressful conditions within the host.

Structural and Biophysical properties of therapeutically important proteins Rv1509 and Rv2231A of Mycobacterium tuberculosis.

Through comparative analyses using BLASTp and BLASTn of the 25 target sequences, our research identified two unique post-transcriptional modifiers, Rv1509 and Rv2231A, which serve as distinctive and characteristic proteins of M.tb - the Signature Proteins. Here, we have characterized these two signature proteins associated with pathophysiology of M.

Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing.

MycoVarP: Mycobacterium Variant and Drug Resistance Prediction Pipeline for Whole-Genome Sequence Data Analysis.

Whole-genome sequencing (WGS) provides a comprehensive tool to analyze the bacterial genomes for genotype-phenotype correlations, diversity of single-nucleotide variant (SNV), and their evolution and transmission. Several online pipelines and standalone tools are available for WGS analysis of () complex (MTBC). While they facilitate the processing of WGS data with minimal user expertise, they are either too general, providing little insights into bacterium-specific issues such as gene variations, INDEL/synonymous/PE-PPE (IDP family), and drug resistance from sample data, or are limited to specific objectives, such as drug resistance.

Energetics of Spike Protein Opening of SARS-CoV-1 and SARS-CoV-2 and Its Variants of Concern: Implications in Host Receptor Scanning and Transmission.

The receptor binding domain(s) (RBD) of spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 (severe acute respiratory syndrome coronavirus) undergoes closed to open transition to engage with host ACE2 receptors. In this study, using multi atomistic (equilibrium) and targeted (non-equilibrium) molecular dynamics simulations, we have compared energetics of RBD opening pathways in full-length (modeled from cryo-EM structures) S proteins of SARS-CoV-1 and SARS-CoV-2. Our data indicate that amino acid variations at the RBD interaction interface can culminate into distinct free energy landscapes of RBD opening in these S proteins.

Methyltransferase Rv1515c Can Suppress Host Defense Mechanisms by Modulating Immune Functions Utilizing a Multipronged Mechanism.

() gene encodes a conserved hypothetical protein exclusively present within organisms of MTB complex and absent in non-pathogenic mycobacteria. analysis revealed that Rv1515c contain S-adenosylmethionine binding site and methyltransferase domain. The DNA binding and DNA methyltransferase activity of Rv1515c was confirmed .

Macrophage: A Cell With Many Faces and Functions in Tuberculosis.

() is the causative agent of human tuberculosis (TB) which primarily infects the macrophages. Nearly a quarter of the world's population is infected latently by . Only around 5%-10% of those infected develop active TB disease, particularly during suppressed host immune conditions or comorbidity such as HIV, hinting toward the heterogeneity of infection.

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.

The exploitation of host autophagy and ubiquitin machinery by in shaping immune responses and host defense during infection.

Intracellular pathogens have evolved various efficient molecular armaments to subvert innate defenses. Cellular ubiquitination, a normal physiological process to maintain homeostasis, is emerging one such exploited mechanism. Ubiquitin (Ub), a small protein modifier, is conjugated to diverse protein substrates to regulate many functions.

A case of adult-onset ophthalmoplegic migraine.

Ophthalmoplegic migraine (OM) also called recurrent painful ophthalmoplegic neuropathy (RPON) is not a so common disorder. It is characterized by childhood onset, ophthalmoplegia and migraine type of headache. The most common involved nerve is third cranial nerve.

Role of multiple factors likely contributing to severity-mortality of COVID-19.

COVID-19 stalled the world in 2020 and continues to be the greatest health crisis of this generation. While the apparent case fatality rates across fluctuates around ~2% globally, associated mortality/death rate (deaths per million population) varies distinctly across regions from the global average of ~600 per million population. Heterogeneous factors have been linked with COVID-19 associated mortalities and these include age, share of geriatric population, comorbidities, trained immunity and climatic conditions.

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.

Bacteria Expressing -Specific Rv1954A Induce Macrophage Activation and Modulate the Immune Response.

(), the intracellular pathogen causing tuberculosis, has developed mechanisms that endow infectivity and allow it to modulate host immune response for its survival. Genomic and proteomic analyses of non-pathogenic and pathogenic mycobacteria showed presence of genes and proteins that are specific to . studies predicted that Rv1954A is a hypothetical secretory protein that exhibits intrinsically disordered regions and possess B cell/T cell epitopes.

Immunodominant Protein Rv1507A Elicits Th1 Response and Modulates Host Macrophage Effector Functions.

() persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. comparative genomic analysis of Mycobacterium species identified Rv1507A as a "signature protein" found exclusively in .

Protein promiscuity in drug discovery, drug-repurposing and antibiotic resistance.

Proteins are supposed to bind to their substrates/ligands in a specific manner via their pre-formed binding sites, according to classical biochemistry. In recent years, several types of deviations from this norm have been observed and called promiscuous behavior. Enzymatic promiscuities allow several biochemical functions to be carried out by the same enzyme.

Peptidyl-prolyl isomerase-B is involved in biofilm formation and a generic target for drug repurposing-based intervention.

Tuberculosis (TB), a disease caused by (), takes one human life every 15 s globally. Disease relapse occurs due to incomplete clearance of the pathogen and reactivation of the antibiotic tolerant bacilli. , like other bacterial pathogens, creates an ecosystem of biofilm formed by several proteins including the cyclophilins.

Protein adaptations in extremophiles: An insight into extremophilic connection of mycobacterial proteome.

The biological paradox about how extremophiles persist at extreme ecological conditions throws a fascinating picture of the enormous potential of a single cell to adapt to homeostatic conditions in order to propagate. Unicellular organisms face challenges from both environmental factors and the ecological niche provided by the host tissue. Although the existence of extremophiles and their physiological properties were known for a long time, availability of whole genome sequence has catapulted the study on mechanisms of adaptation and the underlying principles that have enabled these unique organisms to withstand evolutionary and environmental pressures.