Genomic diversity in the critical priority pathogen Klebsiella pneumoniae: global and regional perspectives

Klebsiella pneumoniae (Kpn) is a hospital-acquired pathogen of critical importance due to extensive resistance to last-resort antibiotics like carbapenems and colistin. The emergence of hypervirulence and its convergence with antibiotic resistance in some Kpn lineages is a public health threat. Understanding the regional prevalence of different lineages of Kpn and their resistomes and virulomes, in the backdrop of global data, will be valuable in tackling Kpn infections. A collection of 22,569 publicly available genomes of human Kpn isolates, from 83 countries, including the genomes of 11 Kpn isolates sequenced in this study, was analyzed. Sequence-, capsular-, O-antigen-types, antibiotic resistance, and virulence factor genes were predicted from the genome sequences using the Kleborate module on PathogenWatch, and their prevalence across 10 geographical regions was assessed. In addition, the global and regional prevalence of convergent isolates carrying both hypervirulence and antibiotic resistance genes was also determined. The sublineages SL258, SL147, SL17, SL15 and SL307 were the top 5 most prevalent globally. Regionally prevalent, but problem sequence types such as ST231, ST512, ST16, ST2096, and ST17 were identified and were often found to carry distinct virulomes and resistomes. Kpn was found to have very high capsular type diversity, but a lower O-antigen diversity. Worldwide, predicted resistance to carbapenems among Kpn was at 66.79% (95% CI:66.17–67.40), while that for colistin was 7.01% (CI:6.68–7.35). Relative to other regions, the carriage of the hypervirulence-associated siderophore aerobactin was significantly higher in India (OR:3.53, p < 2.2e-16) as was the carriage of the genotoxin colibactin in South America (OR:4.78, p < 2.2e-16) and in North & Central America (OR:5.99, p < 2.2e-16). The convergence of yersiniabactin and aerobactin carriage with predicted carbapenem resistance in Kpn was significantly higher (OR:4.2, p < 2.2e-16) in Myanmar, Nepal, Bangladesh, Pakistan and China (countries around India) and in India (OR:3.53, p < 2.2e-16) relative to other regions. Our study highlights the enormous genomic diversity in Kpn. Research, infection control measures, antibiotic susceptibility testing and treatment regimens should consider regionally-prevalent problem sequence types, which often carry distinct resistomes and virulomes. Vaccine development targeting the less diverse O-antigen, rather than the capsular antigen, could yield better coverage.