Antibiotic Resistance, Tolerance, and Persistence in Healthcare-Associated Bacterial Pathogens: Mechanisms, Evolution, and Clinical Opportunities

Antibiotic resistance in healthcare-associated bacterial pathogens remains a critical global health threat, especially in hospital and long-term facilities where vulnerable patients experience severe, recurrent, and difficult-to-treat infections. Many opportunistic pathogens exhibit multidrug resistance, prolonged persistence in hospital environments, and the capacity for nosocomial transmission and outbreaks. Well-known resistance phenotypes arise through antibiotic inactivation, target modification, reduced permeability, active efflux, biofilm-associated tolerance, and persistence. Disentangling how these diverse mechanisms emerge, interact, and evolve under clinical pressure is essential for improving infection control, surveillance, and novel therapeutic strategies.This Research Topic aims to advance a mechanistically rigorous and clinically relevant understanding of antibiotic resistance, tolerance, and persistence in healthcare-associated bacterial pathogens. We particularly welcome contributions that move beyond descriptive cataloging of resistance determinants to define causal mechanisms, quantify resistance-related phenotypes, and link molecular findings to clinical outcomes, treatment failure, and transmission risk. Contributions that clarify the distinction and interactions between genetic resistance, tolerance, persistence, and heteroresistance are especially welcome.We seek to integrate studies that characterize the full spectrum of resistance mechanisms, and their regulation in response to antibiotic exposure, host factors, and healthcare environments. Genome-informed approaches, such as whole genome sequencing, comparative genomics, transcriptomics, proteomics, metabolomics, and structural biology, are encouraged where they provide functional insight into how resistance is deployed as part of the pathogenicity repertoire in the clinic. A central goal is to bridge basic mechanisms with clinical applications, linking resistance determinants to therapeutic decision-making, patient outcomes, chronic or device-associated infections, and nosocomial transmission dynamics. Studies that identify exploitable vulnerabilities associated with resistance, such as collateral sensitivity, fitness trade-offs, or context-dependent susceptibility, are particularly encouraged. Themes of interest may include, but are not limited to:• Original research on enzymatic resistance mechanisms (e.g., β-lactamases, aminoglycoside-modifying enzymes) and their impact on multidrug resistance in healthcare-associated bacteria.• Comparative genomic and genome-wide association studies linking specific resistance genes, regulatory elements, and mobile genetic elements (plasmids, transposons, phages) to clinical resistance phenotypes.• Investigations into biofilm formation, surface persistence, and tolerance or persistence phenotypes as drivers of chronic and device-associated infections in healthcare settings.• Experimental and clinical studies disentangling genetic resistance from tolerance and persistence, including heteroresistance and phenotypic switching.• Research on the interplay between multiple resistance mechanisms (e.g., enzymatic degradation, efflux, target modification, reduced permeability) and their combined effects on fitness, virulence, and spread.• Experimental infection models (in vitro or in vivo) assessing how resistance mechanisms influence virulence, immune evasion, and response to antimicrobial therapy.• Methods and technology papers presenting new tools, assays, or computational approaches for detecting, quantifying, or predicting antibiotic resistance determinants in clinical isolates.• Reviews or mini-reviews summarizing current knowledge on antibiotic resistance mechanisms in healthcare-associated bacterial pathogens, highlighting therapeutic opportunities and knowledge gaps. Topic editors: Daniel Pletzer, Jennifer Marie Colquhoun, Juan Xicohtencatl-Cortes, Sanjay Gautam Source: https://www.frontiersin.org/research-topics/76885/antibiotic-resistance-tolerance-and-persistence-in-healthcare-associated-bacterial-pathogens-mechanisms-evolution-and-clinical-opportunities