Molecular mimicry in the agroecosystem: A new paradigm for understanding how pesticide residues drive the emergence of antimicrobial resistance

Antimicrobial resistance (AMR) is a mounting global crisis, with environmental dissemination of antibiotic resistance genes (ARGs) emerging as a critical driver. Agroecosystems, chronically exposed to complex mixtures of bioactive chemicals, including pesticides, represent an underrecognized hotspot for AMR evolution. This review synthesizes established mechanisms by which pesticides select for resistance and introduces a novel hypothesis: molecular mimicry as a hidden driver. Evidence highlights three key pathways: cross-resistance via multidrug efflux pumps; coselection on mobile genetic elements; and enhanced horizontal gene transfer under pesticide-induced stress. Structural similarities may cause bacterial defense systems to misidentify pesticide molecules as antimicrobial threats, triggering resistance responses analogous to endocrine disruption by xenoestrogens such as BPA and DDT. Case studies on macrolides and ivermectin illustrate this concept, as both share macrocyclic lactone scaffolds with insecticides like spinosyns. This framework positions pesticide pollution as a central contributor to AMR, underscoring the need for One Health-based regulatory reform.