Genomic analysis of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli colonising adults in Blantyre, Malawi reveals previously undescribed diversity

Abstract

Escherichia coli is a ubiquitous bacterial species, associated with drug resistant infections; hundreds of thousands of genomes are now available, but are biased towards high-income countries and clinical isolates. Data from sub-Saharan Africa (sSA) are underrepresented in global sequencing efforts and may represent a major source of genetic diversity with respect to transmissible antimicrobial resistance (AMR). We carried out a genomic investigation of extended-spectrum beta-lactamase (ESBL)-producing E. coli colonising adults in Blantyre, Malawi to assess the diversity and AMR determinants and to place these isolates in the context of globally available genomes. We carried out short-read whole-genome sequencing of 473 colonising ESBL E. coli isolated from stool and placed them in the context of a previous curated species wide collection of 10,146 isolates using the popPUNK clustering algorithm and by constructing a core gene phylogeny. The most frequently identified STs in Malawian isolates were the globally successful ST131 and ST410, and blaCTX-M were the dominant ESBL genes, mirroring global trends. However, 37% of Malawian isolates did not cluster with any isolates in the global collection, and the core gene phylogeny was consistent with local subclades including in ST410 and several phylogroup A lineages. Apparent undescribed diversity in Malawian E. coli could be due to local selection pressures or sampling biases in global E. coli collections. Taking a one health approach to further sampling of E. coli from Malawi and sSA, and principled incorporation into unbiased global collections is necessary to understand local, regional and global transmission of both E. coli and priority AMR genes. Data Summary All data and code to replicate this analysis is available as the blantyreESBL v1.0.0 R package (https://doi.org/10.5281/zenodo.5554082) available at https://github.com/joelewis101/blantyreESBL. Reads from all isolates sequenced as part of this study have been deposited in the European Nucleotide Archive, and accession numbers (as well as accession numbers of publicly available genomes used in this analysis) are provided in the R package.