Discovery and Synergy: Novel Antimicrobial Compounds and Combinations Against Resistance

Antimicrobial resistance (AMR) is steadily eroding the reliability of routine infection management across clinical and veterinary settings, turning once-treatable diseases into persistent, relapsing, and harder-to-control conditions. This challenge is amplified by the continued emergence and spread of high-risk pathogens across healthcare and community environments, the complexity of host–pathogen interactions, and the limited pace of therapeutics entering the pipeline. AMR is inherently tied to understanding causal agents, pathogenicity mechanisms, transmission routes, and the design of prevention and treatment strategies that measurably improve infectious disease outcomes in humans and animals.This Research Topic focuses on an integrated, mechanism-forward strategy to counter AMR: discovering and characterizing novel antimicrobial compounds from biological and chemical sources and systematically identifying synergistic combinations that restore or enhance activity against resistant pathogens. Contributions should move beyond efficacy-only observations to explain how candidates and combinations act—via impacts on microbial metabolism, cell structure, virulence programs, and stress responses—supported by experimentation such as high-throughput screening, genome-informed analyses, transcriptomics/proteomics, and advanced in vitro and in vivo infection models. The goal is to expand the repertoire of actionable anti-infective options while enabling rational, evidence-based optimization of combination therapies aligned with infection prevention and treatment priorities.To advance investigations that address AMR organisms, the collection will include but is not limited to the following areas.• Discovery and purification of antimicrobial molecules from underexplored microbial, plant, or marine sources with validated activity against priority resistant pathogens• Structure–activity relationship mapping and medicinal chemistry optimization to improve potency, stability, and pathogen selectivity• Systematic synergy screening of antibiotic–antibiotic, antibiotic–adjuvant, or antimicrobial–phytochemical combinations against MDR/XDR clinical isolates• Mechanistic dissection of synergy showing multi-target disruption (e.g., membrane permeabilization enabling intracellular target engagement)• Virulence-targeting or anti-adhesion approaches that reduce disease severity while limiting selection for resistance• Host–pathogen interaction studies revealing how candidate antimicrobials reshape immune evasion, colonization, or tissue damage• In vivo validation in relevant infection models• Studies on resistance evolution under monotherapy vs combination therapy, including genomic trajectories and fitness trade-offs• Rapid molecular/antigenic assays to guide targeted antimicrobial combinations for infections• Antimicrobial coating using small molecules to prevent microbial biofilm formation and colonization. Topic editors: Samantha Flores-Treviño, Lewis Oscar Felix Raj Lucas, Alvaro Mourenza Flórez Source: https://www.frontiersin.org/research-topics/80965/discovery-and-synergy-novel-antimicrobial-compounds-and-combinations-against-resistance