ABSTRACTAcanthamoeba
species are among the most common free-living amoeba and ubiquitous protozoa, mainly distributed in water and soil, and cause
Acanthamoeba
keratitis (AK) and severe visual impairment in patients. Although several studies have reported genomic characteristics of
Acanthamoeba
, limited sample sizes and sources have resulted in an incomplete understanding of the genetic diversity of
Acanthamoeba
from different sources. While endosymbionts exert a significant influence on the phenotypes of
Acanthamoeba
, including pathogenicity, virulence, and drug resistance, the species diversity and functional characterization remain largely unexplored. Herein, our study sequenced and analyzed the whole genomes of 19
Acanthamoeba
pathogenic strains that cause AK, and by integrating publicly available genomes, we sampled 29
Acanthamoeba
strains from ocular, environmental, and other sources. Combined pan-genomic and comparative functional analyses revealed genetic differences and evolutionary relationships among the different sources of
Acanthamoeba
, as well as classification into multiple functional groups, with ocular isolates in particular showing significant differences that may account for differences in pathogenicity. Phylogenetic and rhizome gene mosaic analyses of ocular
Acanthamoeba
strains suggested that genomic exchanges between
Acanthamoeba
and endosymbionts, particularly potential antimicrobial resistance genes trafficking including the
adeF
,
amrA
, and
amrB
genes exchange events, potentially contribute to
Acanthamoeba
drug resistance. In conclusion, this study elucidated the adaptation of
Acanthamoeba
to different ecological niches and the influence of gene exchange on the evolution of ocular
Acanthamoeba
genome, guiding the clinical diagnosis and treatment of AK and laying a theoretical groundwork for developing novel therapeutic approaches.
IMPORTANCEAcanthamoeba
causes a serious blinding keratopathy,
Acanthamoeba
keratitis, which is currently under-recognized by clinicians. In this study, we analyzed 48 strains of
Acanthamoeba
using a whole-genome approach, revealing differences in pathogenicity and function between strains of different origins. Horizontal transfer events of antimicrobial resistance genes can help provide guidance as potential biomarkers for the treatment of specific
Acanthamoeba
keratitis cases.