Faecal carriage of ESBL-producing Escherichia coli in a remote region of Niger

Background Data on extended-spectrum β--lactamase-producing Escherichia coli (ESBL-E. coli) carriage in community settings, especially in developing countries, are scarce. Here, we describe the population structure and molecular characteristics of resistance of ESBL-E. coli faecal isolates in a rural African population. Methods and findings Between April and May 2017, stools of 383 healthy participants were collected from 20 villages in rural Southern Niger during a clinical trial on ciprofloxacin prophylaxis carried out during a meningococcal meningitis outbreak. Of 383 individuals, 354 (92.4%) were carriers of ESBL-E. coli before any ciprofloxacin intake. A subset of 90 of these ESBL-E. coli containing stools were selected for further analysis, from which 109 different ESBL-E. coli were recovered and whole genome sequenced by short-(Illumina) and long-(Nanopore) reads. Most belonged to the commensal-adapted phylogroup A (91, 83.5%), with high clonal diversity (57 distinct clones). One-quarter harboured the high pathogenicity island previously associated with a longer duration of faecal carriage. The blaCTX-M-15 gene was the major ESBL determinant (107, 98.1%). It was chromosome-integrated in approximately half of the cases (48, 44.9%), at multiple integration sites in diverse chromosomal genetic backgrounds. When plasmid-borne, blaCTX-M-15 was found in a large diversity of incompatibility groups. A single genetic background was found for 20 distinct plasmids, whereas very closely related plasmids were found in different genetic backgrounds in six cases, suggesting plasmid spread among strains. No geographical or social links to resistance patterns were observed. Conclusions Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger without apparent antibiotic selective pressure. E. coli were highly diverse, well adapted commensal strains, with chromosomal integration of CTX-M-15 encoding gene in almost half of the cases. Evidence of clonal and plasmid spread suggest a risk of sustainable implementation in community faecal carriage. Author Summary Community faecal carriage of extended-spectrum β--lactamase-producing Escherichia coli (ESBL-E. coli) increased alarmingly over the past two decades. Nevertheless, data on ESBL-E. coli carriage in community settings are scarce, especially in developing countries, yet fundamental to be able to implement specific strategies to prevent their spread and determine adequate empiric antibiotic therapies. We conducted an ancillary study focusing on ESBL-E. coli carriage during a clinical trial on meningitis prophylaxis in rural Southern Niger. Almost all subjects were ESBL-E. coli carriers despite the apparent absence of recent antibiotic use. Using whole genome sequencing, we found a wide diversity of E. coli isolates well adapted to commensal lifestyle and bearing the blaCTX-M-15 gene located either on the chromosome or on a variety of plasmids, some spreading between clones. ESBL-E. coli isolates are endemic and well implanted in this community setting. Identification of the selective pressures involved should be a priority.