Stress-Induced Plant Specialized Metabolism: Signaling, Multi-Omics Integration, and Plant-Derived Antimicrobial Metabolites to Combat Antimicrobial Resistance

Antimicrobial resistance (AMR) is one of the major health threats of the 21st century and demands innovative sources of bioactive compounds. In 2019, infections caused by resistant bacteria directly accounted for 1.27 million deaths and contributed to an additional 4.95 million associated deaths, underscoring the urgency of exploring new strategies. Among emerging alternatives, specialized plant metabolites stand out, as their biosynthesis is enhanced under biotic or abiotic stress. These stimuli increase reactive oxygen species (ROS), activate cascades regulated by mitogen-activated protein kinases (MAPKs), and trigger defense-related hormonal pathways involving salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA), which in turn regulate transcription factors and biosynthetic modules, promoting the accumulation of compounds with antimicrobial activity. In this review, we synthesize recent literature (2020-2025) with emphasis on studies that report quantitative activity metrics. We integrate evidence linking stress physiology and metabolite production, summarize mechanisms of action, and propose a conceptual multi-omics pipeline, synthesized from current best practices, that combines RNA sequencing and LC/GC-MS-based metabolomics with bioinformatic tools to prioritize candidates with antimicrobial potential. We discuss elicitation strategies and green extraction, highlight bryophytes (e.g., <i>Pseudocrossidium replicatum</i>) as a differentiated chemical source, and explore citrus Huanglongbing (HLB) as a translational case study. We conclude that integrating stress physiology, multi-omics, and functional validation can accelerate the transition of stress-induced metabolites toward more sustainable and scalable medical and agricultural applications.