Antivirulence Strategies Targeting Secretion Systems and Toxin Delivery in Vibrio and Enteric Pathogens: Mechanisms, Immune Repair Readouts, and Translational Development

Enteric bacterial infections remain a major global health burden, contributing to acute diarrheal disease, outbreaks linked to food and water exposure, and severe complications in vulnerable populations. Vibrio spp. (including V. cholerae and related species) and other enteric pathogens also impose increasing pressure on public health systems due to antimicrobial resistance, limited access to supportive care in many settings, and the persistent challenge of preventing transmission and reinfection. These realities strengthen the case for antivirulence approaches—therapeutics designed to disarm pathogens by blocking host-directed virulence functions rather than inhibiting bacterial growth alone.A growing body of work shows that enteric pathogens use type III and type VI secretion systems (T3SS/T6SS) and secreted toxins to manipulate host defenses at key mucosal sites. Instead of acting only through proliferation, pathogens can reprogram epithelial and immune cell functions, compromise barrier and antimicrobial programs, and alter inflammatory signaling to promote colonization, persistence, and spread. However, important knowledge gaps remain in (i) how secretion system effectors and toxins act in coordinated and time-resolved ways at the epithelial interface, (ii) how these activities reshape innate and adaptive immunity across tissues and cell types, and (iii) which host and microbial nodes are most actionable for therapeutic “immune repair”—restoring protective function without broad immunosuppression.This Research Topic will cover key areas of research spanning mechanistic infection biology through translational development, with emphasis on secretion system- and toxin-driven immune modulation in Vibrio and other enteric pathogens, and how these insights can guide targeted antivirulence interventions that complement antibiotics and vaccines.We welcome articles addressing, but not limited to, the following themes:-Mechanistic studies on T3SS/T6SS architecture, regulation, effector repertoires, and toxin delivery in Vibrio spp. and other enteric pathogens.-Spatial and temporal mapping of effector and toxin activity at the epithelial interface, including colonization niches and host cell-type specificity.-Host epithelial barrier disruption and repair, including tight junction remodeling, cytoskeletal changes, epithelial restitution, and permeability control during infection.-Remodeling of mucus defenses and antimicrobial peptide programs, including goblet cell responses and microbiota-linked effects on mucosal protection.-Rewiring of host inflammatory signaling networks (e.g., NF-κB, MAPK, and related pathways) that shape early mucosal immune responses and disease outcomes.-Modulation of intracellular sensing and interferon-associated programs, including mechanisms that suppress, misdirect, or exploit host antimicrobial states.-Inflammasome regulation and cell-death pathway control (including pyroptosis), and the consequences for persistence, dissemination, and tissue damage.-Manipulation of autophagy, vesicular trafficking, and antigen processing pathways, including effects on immune activation and inflammatory tone.-Disruption of myeloid cell antimicrobial functions, including phagosome maturation, phagolysosomal killing, and pathogen clearance despite immune recruitment.-Translational antivirulence strategies and “immune repair” readouts, including secretion/effector inhibitors, host-directed restoration metrics, and combination approaches with antibiotics and/or vaccines. Topic editors: Ariadna Thalia Bernal Mercado, Mohsan Ullah Goraya, Francisco Javier Vazquez-Armenta Source: https://www.frontiersin.org/research-topics/76865/antivirulence-strategies-targeting-secretion-systems-and-toxin-delivery-in-vibrio-and-enteric-pathogens-mechanisms-immune-repair-readouts-and-translational-development