Infectious diseases remain one of the greatest global health challenges, with bacteria, viruses, and fungi continually evolving strategies to survive, disseminate, and evade host defenses. Despite their evolutionary distance, pathogens share conserved tactics: subversion of host cell death pathways, hijacking of autophagy, escape from neutrophil extracellular traps (NETs), and manipulation of host epigenetic and post-translational machinery. These interactions not only ensure pathogen survival but also reprogram host immunity, often tilting the balance toward persistent infection, tissue pathology, or systemic disease.

Traditional antimicrobial development has focused primarily on targeting the pathogen directly. However, the rapid rise of antimicrobial resistance (AMR), the emergence of novel viral pandemics, and the increasing incidence of invasive fungal infections underscore the urgent need for innovative strategies that move beyond pathogen-directed approaches. Host-directed therapies (HDTs) offer such a paradigm shift: instead of attacking the microbe, they aim to restore or enhance host pathways disrupted by infection.

At the core of this effort lies the systematic understanding of host–pathogen crosstalk. By mapping how pathogens interfere with programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), autophagy, and innate immune defenses such as NETosis, we can identify crucial molecular nodes exploited across kingdoms. Furthermore, advances in multi-omics, CRISPR-based functional screens, and structural biology now allow us to decode pathogen-induced epigenetic remodeling, including DNA methylation, histone modifications, SUMOylation, and ADP-ribosylation. These insights reveal both conserved vulnerabilities and pathogen-specific interventions that can be translated into therapeutic and diagnostic innovations.

This Research Topic aims to assemble cutting-edge research and authoritative reviews that collectively illuminate the multidimensional tug-of-war between host and pathogen across bacteria, viruses, and fungi. By bridging disciplines and kingdoms, this collection seeks to accelerate the discovery of novel host targets, enhance our mechanistic understanding of infection biology, and open avenues for next-generation host-directed therapies.

In this article collection, we consider the following sub-topics:

• Host–pathogen interaction mechanisms driving antimicrobial resistance

• Immunomodulating drugs and host-directed therapies against resistant pathogens

• Pathogen manipulation of host cell death pathways (apoptosis, pyroptosis, necroptosis, ferroptosis)

• Autophagy regulation in antimicrobial resistance and pathogen persistence

• Neutrophil extracellular traps (NETs) and pathogen evasion mechanisms

• Epigenetic reprogramming of host immunity by resistant pathogens

• Role of virulence factors in pathogen's survival inside host

• Identification of novel host targets using CRISPR and multi-omics approaches

• Technological advances to study AMR-related host responses

• Translational and clinical aspects of host-directed therapies for AMR

In this Research Topic we welcome the following article types: Original Research, Review, Mini Review, Perspective and Methods.

Are you interested in contributing a manuscript to this Research Topic?

Host–Pathogen Crosstalk: Survival Strategies, Immune Evasion, and Host-Directed Targets in Bacterial, Viral, and Fungal Infections