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

Boas C L van der Putten; Jarne M van Hattem; John Penders; Combat Consortium; Daniel R Mende; Constance Schultsz

doi:10.1099/acmi.0.000541.v4

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

Access Microbiol. 2024 Feb 12;6(2):000541.v4. doi: 10.1099/acmi.0.000541.v4. eCollection 2024.

Authors

Boas C L van der Putten^{1

2

3}, Jarne M van Hattem¹, John Penders^{4

5}, Combat Consortium¹, Daniel R Mende¹, Constance Schultsz^{1

2}

Affiliations

¹ Department of Medical Microbiology, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
² Department of Global Health, Amsterdam UMC location University of Amsterdam, Amsterdam Institute for Global Health and Development, Meibergdreef 9, Amsterdam, The Netherlands.
³ Present address: Centre for Infectious Diseases Research, Diagnostics and Laboratory Surveillance, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
⁴ School for Public Health and Primary Care (Caphri), Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, Netherlands.
⁵ School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, Netherlands.

Abstract

Objectives: Extended-spectrum β-lactamase-producing Escherichia coli (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 E. coli (ExPEC) are significantly more likely to persist than other E. coli lineages. The long-term carriage of E. coli from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D E. coli.

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.

Keywords: ESBL; Escherichia coli; antimicrobial resistance; travel; whole genome sequencing.