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

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.