Recombination and diversifying selection drive the adaptive evolution of tet(X)-Positive Escherichia coli

Eur J Clin Microbiol Infect Dis. 2026 Jul 17. doi: 10.1007/s10096-026-05592-4. Online ahead of print.

Abstract

Objectives: This study aimed to characterize the population structure, recombination landscapes and diversification patterns of global tet(X)-positive Escherichia coli.

Methods: We conducted phylogenomic, recombination and diversifying selection analyses on 1721 global tet(X)-positive E. coli genomes.

Results: These isolates were primarily distributed in China (72.7%) and most carried tet(X4) variant (97.5%), with phylogroups A (61.4%) and B1 (26.8%) as the most prevalent. Significant positive correlations were observed in tet(X4) with IncHI1A/IncHI1B plasmid and ISVsa3, blaCTX-M-65 with IncI and blaOXA-181 with IncX3. Phylogenetic analysis identified cluster 17 (30.6%) and cluster 7 (17.7%) as the most prevalent lineages, among which some isolates co-harboring tet(X) with blaCTX-M, blaNDM, and blaOXA exhibited high genetic similarity (< 20 SNPs) across different countries, demonstrating potential clonal transmission. High-recombination regions (HRRs) were enriched in metabolic pathways, two-component systems, and biofilm formation, while Cluster 17 uniquely harbored aromatic compound degradation. Lineage-specific mutation patterns in HRRs included transporters and amino acid-related enzymes in cluster 17 and two-component systems in cluster 7. Genes under diversifying selection in non-recombinant regions mainly enriched in flagellar assembly and bacterial motility, alongside cluster-specific enrichment of motility functions and transporters in cluster 17 and cellular signaling in cluster 7, reflecting virulence, host interaction and immune evasion. Prophage-encoded genes were predominantly categorized as defense mechanisms, signal transduction, stress responses and metabolic functions that enhance bacterial fitness in fluctuating environments.

Conclusions: The adaptive evolution of tet(X)-positive E. coli is cooperatively driven by horizontal gene transfer, clonal expansion and diversifying selection, underscoring an urgent need for global genomic surveillance.

Keywords: Escherichia coli; tet(X); Diversifying selection; Evolutionary dynamics; Recombination; Tigecycline resistance.