Acanthamoeba as a microbial Trojan horse: intracellular endosymbionts, adaptive immune evasion and antimicrobial resistance dissemination from a one health perspective

Abstract

Antimicrobial resistance (AMR) is a global public health crisis driven not only by clinical antibiotic misuse but also by environmental reservoirs that remain insufficiently characterized. Free-living amoebae of the genus Acanthamoeba are ubiquitous eukaryotic protists that graze on diverse bacterial communities via phagocytosis, yet certain clinically important pathogens—including Legionella pneumophila , Mycobacterium spp. and Pseudomonas aeruginosa —have evolved sophisticated mechanisms to survive and replicate within the amoebal phagosome. This intracellular niche serves simultaneously as an evolutionary training ground for bacterial virulence and immune evasion, a physical shelter against environmental biocides, and a hotspot for horizontal gene transfer (HGT) of resistance determinants. Strikingly, the molecular strategies used to subvert amoebal killing are mechanistically conserved with those deployed against human macrophages, effectively shielding amoeba-trained bacteria from both innate and adaptive immune clearance. Recent studies demonstrate that Acanthamoeba -associated bacteria exhibit significantly elevated multidrug resistance indices compared with free-living counterparts, that plasmid-borne carbapenem-resistance genes can transfer between co-ingested species within the phagosome, and that the highly resistant cyst stage shields intracellular bacteria from chlorine disinfection at concentrations exceeding water-treatment standards. This review provides a comprehensive synthesis of the molecular and immunological mechanisms underlying intracellular bacterial survival within Acanthamoeba , evaluates the evidence for AMR amplification through protist–bacteria interactions, and frames these processes within the One Health paradigm connecting environmental reservoirs to clinical and veterinary outcomes.