Extra-intestinal pathogenic lineages of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli are associated with prolonged ESBL gene carriage

OBJECTIVES: Extended-spectrum ß-lactamase-producing (ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveller cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage after recent acquisition. We aimed to identify which ESBL-Ec lineages are associated with increased carriage duration after return from international travel. METHODS: In a prospective cohort study of 2001 international travellers, we analysed 160 faecal ESBL-Ec isolates from all 38 travellers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travellers, we confirmed the long-term carriage of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (=12 months of carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month of carriage). Long-read sequencing was employed to investigate long-term ESBL plasmid carriage. RESULTS: We show that in healthy travellers with very low antibiotic usage, extra-intestinal pathogenic lineages of (ExPEC) are significantly more likely to persist than other lineages. The long-term carriage of from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D . CONCLUSIONS: Although ExPEC lineages frequently cause extra-intestinal infections such as bloodstream infections, our results indicate that ExPEC lineages are also efficient intestinal colonizers, which potentially contributes to their onward transmission.