Genomic and antigenic diversity of carried Klebsiella pneumoniae isolates mirrors that of invasive isolates in Blantyre, Malawi

Klebsiella pneumoniae is an antimicrobial resistance (AMR) associated pathogen of global importance, and polyvalent vaccines targeting K. pneumoniae O-antigens are in development. Genomes from sub-Saharan Africa (sSA) are underrepresented in global sequencing efforts. We therefore carried out a genomic analysis of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae complex isolates colonising adults in Blantyre, Malawi, placed these isolates in a global genomic context, and compared colonising to invasive isolates from the main public hospital in Blantyre. 203 isolates from stool and rectal swabs from adults were whole-genome sequenced and compared to a publicly available multicountry collection of 484 K. pneumoniae genomes sampled to cover maximum diversity of the species, 150 previously sequenced Malawian and 66 Kenyan isolates from blood or sterile sites. We inferred phylogenetic relationships and analysed the diversity of genetic loci linked to AMR, virulence, capsule (K-) and LPS O-antigen (O-types). We find that the diversity of Malawian Klebsiella isolates is representative of the species’ population structure, but with local success and expansion of sequence types (STs) ST14, ST15, ST340 and ST307. Siderophore and hypermucoidy genes were more frequent in invasive versus carriage isolates (present in 13% vs 1%, p < 0.001) but still generally lacking in most invasive isolates. The population structure and distribution of O-antigen types was similar in Malawian invasive and carriage isolates, with O4 being more common in Malawian isolates (14%) than in previously published studies (2-5%). We conclude that host factors, pathogen opportunity or alternate virulence loci not linked to invasive disease elsewhere are likely to be the major determinants of invasive disease in Malawi. Distinct ST and O-type distributions in Malawi highlights the need for geographically aware sampling to robustly define secular trends in Klebsiella diversity. Colonising and invasive isolates in Blantyre are similar and hence O-typing of colonising Klebsiella isolates may be a rapid and cost-effective approach to describe global diversity and guide vaccine development.Data SummaryAll 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.