The spread of CTX-M-type extended-spectrum beta-lactamases in China: Epidemiology and evolutionary analyses

CTX-M-type extended-spectrum beta-lactamases (ESBLs) have shown a high level of global transmission, with limited systematic understanding of their epidemic patterns in China. A comprehensive analysis covering 1974-2023 identified 133 (3.2%) bla_CTX-Ms-producing strains among 4146 strains from 25 Chinese cities across 82 genera were performed. Integrating with public database strains (n=431), the study comprised 564 bla_CTX-Ms-positive isolates sourced from 19 provinces (1986-2022) including 300 (53.2%) clinical and 228 (40.4%) environmental bla_CTX-Ms. The most frequent sources of infection were diarrhea (44%), upper respiratory tract infection (22.2%) and urinary tract infection (14%). Phylogenetic studies indicated CTX-M-1 and CTX-M-9 emerged as the predominant subgroups. Lineages exhibited diverse mutation sites without being restricted by geographical conditions. Ka/Ks ratio distribution varied significantly among lineages (P<0.05). Lineages 1 (L1) and L2 were characterized by neutral or purifying selection, whereas L3 was mainly under purifying selection. Adaptive evolution was noted at different loci within each lineage. The influence of geographic distance on phylogeny varied distinctly across different lineages. Notably, for Lineage L3, there was a remarkably strong correlation observed, which implies that human activities exerted a more substantial influence on genetic distances compared to geography. This research provides valuable insights into the epidemiology, genotypic diversity, and evolutionary traits of bla_CTX-Ms in China, supporting health risk assessment for early warning systems.