Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the limitations of existing medications. The quest for better treatment approaches is driving the research in the field of host epigenomics forward in context with tuberculosis. The interplay between various host epigenetic factors and the pathogen is under investigation. A comprehensive understanding of how Mycobacterium tuberculosis orchestrates such epigenetic factors and favors its survival within the host is in increasing demand. The modifications beneficial to the pathogen are reversible and possess the potential to be better targets for various therapeutic approaches. The mechanisms, including histone modifications, DNA methylation, and miRNA modification, are being explored for their impact on pathogenesis. In this article, we are deciphering the role of mycobacterial epigenetic regulators on various strategies like cytokine expression, macrophage polarization, autophagy, and apoptosis, along with a glimpse of the potential of host-directed therapies.

Rv1899c, a previously identified HDAC1–ZBTB25-interacting protein of Mycobacterium tuberculosis, plays a crucial role in bacterial adaptation and immune modulation. Recombinant M. smegmatis-expressing Rv1899c (MS_ Rv1899c) showed enhanced survival under acidic and oxidative stress compared to vector controls, along with improved early intracellular growth in THP1-derived macrophages. This was accompanied by reduced reactive oxygen species (ROS), diminished cytokines associated with inflammation and downregulation of autophagy proteins ATG5, Beclin, and LC3, which ultimately skewed the immune response, suppressing the pro-inflammatory M1 macrophage population. Targeting Rv1899c with 3-aminobenzamide (3-AB) impaired intracellular bacterial survival and restored IL-12B expression, while its combination with the HDAC inhibitor C1994 significantly enhanced bacterial clearance. Structural modelling confirmed the high stereochemical quality of the Rv1899c macrodomain, and computational studies identified 3-AB as the strongest ligand (−5.75 kcal/mol), stabilized through hydrogen bonding and hydrophobic interactions with key residues. Molecular dynamics simulations conducted for 200 ns demonstrated stable protein–ligand interactions with consistent parameters, while MM/GBSA analysis indicated favourable binding energy (ΔG_bind = −6.6 kcal/mol), largely influenced by van der Waals and electrostatic forces. Together, these findings highlight Rv1899c as a mediator of stress resistance and immune evasion and propose it as a potential therapeutic target against M. tuberculosis.

Pathogenic microbes utilize virulence strategies to subvert host immune responses, highlighting a continuous race between the pathogen and the host. The emergence of multidrug- resistant and hypervirulent strains of Klebsiella pneumoniae (Kp) poses a critical threat to public health. This critical evaluation identifies key gaps in understanding the interplay between Kp and host innate immunity. This review provides a comprehensive overview of the mechanisms by which Kp triggers various forms of cell death. Dysregulated cell death may exacerbate cytokine release, contributing to the hyperinflammatory response characteristic of sepsis. The rise in antimicrobial resistance (AMR) in Kp necessitates the exploration of alternative therapeutic approaches. This review highlights that immunomodulatory approaches targeting cell death regulators or immune checkpoints may offer host-directed strategies against Kp-induced sepsis. Although novel immunotherapies offer potential to restore immune balance, their clinical applicability remains constrained by limited translational evidence.

Ocular infections are a major cause of morbidity and vision loss worldwide, significantly affecting the quality of life and clinical outcomes. The management of ocular infections has become increasingly difficult due to the rising prevalence of antimicrobial resistance among commonly implicated pathogens. This review summarizes the epidemiology and etiology of ocular infections, with emphasis on bacterial pathogens frequently associated with resistance. Various mechanisms of antimicrobial resistance, including genetic mutations, intrinsic resistance, and biofilm formation, are also discussed. The review further examines the limitations of current therapeutics, such as poor ocular drug penetration, frequent dosing requirements, adverse effects, and reduced efficacy against multi-resistant organisms. In response to these challenges, the need for novel therapeutic approaches with improved stability and prolonged ocular retention is highlighted. Furthermore, the integration of artificial intelligence in ophthalmology is explored, particularly in disease diagnosis, image analysis, treatment planning, and antimicrobial resistance surveillance. Despite these advances, several translational challenges remain, including data set bias, limited external validation, regulatory approval hurdles, data privacy concerns, and restricted accessibility in resource-limited settings, which currently limit the widespread clinical implementation. Therefore, continued surveillance, rational antimicrobial use, and effective therapeutic strategies are essential to reduce the burden of ocular infections and improve patient outcomes.

The mammalian immune system has evolved in constant dialogue with its diverse microbiota, forming an ecological and molecular partnership that is fundamental to health. This review examines how microbial communities shape immunity across developmental and functional axes, the immunological consequences of dysbiosis during infection and inflammatory disease, and emerging microbiota-targeted interventions. The host–microbiota–pathogen triad offers a framework to understand how commensals and pathogens compete for ecological niches and immune recognition, and how disturbances in this balance can cascade into chronic inflammation or infection. Microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan derivatives act as key bioactive intermediaries translating microbial activity into host immune architecture, influencing epigenetic programming, cellular differentiation, and mucosal barrier function. These interactions orchestrate tolerance toward commensals while maintaining effector readiness against pathogens, particularly through regulatory T cell (Treg)–Th17 balance, B cell education, and Immunoglobulin A (IgA) responses. When perturbed, as in infections caused by Clostridioides difficile, Klebsiella pneumoniae, Salmonella enterica , or Listeria monocytogenes , the ensuing dysbiosis reinforces immune dysfunction in a self-perpetuating cycle. Therapeutic frontiers now extend beyond conventional antimicrobial strategies to include live biotherapeutics, bacteriophage therapy, fecal microbiota transplantation, and metabolite-based (postbiotic) interventions. Future efforts must reconcile inter-individual microbiome variability with precision medicine, integrating metagenomic and metabolomic profiling to design safe, effective, and personalized microbiota-centered therapeutics.

Antimicrobial resistance (AMR) has emerged as a critical global health concern that transcends human, animal, and environmental boundaries. The extensive and often indiscriminate use of antibiotics for disease control and growth promotion has accelerated the evolution and spread of resistant pathogens within the aquaculture sector. This review examines aquaculture-associated AMR through a One Health framework. We explore the molecular mechanisms of resistance such as efflux pumps, enzymatic degradation, mobile genetic elements, and horizontal gene transfer that drive the dissemination of antimicrobial resistance genes among aquatic microorganisms. The review synthesizes evidence linking AMR in aquaculture to public health impacts, including the transmission of resistant bacteria through seafood and environmental exposure. Current regulatory measures and stewardship policies are assessed to identify gaps in implementation, particularly in developing regions where enforcement and public awareness remain limited. Review highlights emerging alternatives such as bacteriophage therapy, engineered probiotics, synthetic microbial communities, and CRISPR-based systems as sustainable approaches to reduce antibiotic dependence. Future research priorities include the integration of genomics, artificial intelligence, and environmental DNA monitoring for precision surveillance. This review emphasis the need for cross-sectoral collaboration, innovation, and global policy coherence to mitigate AMR in aquaculture and safeguard food, environmental, and public health security.