Temporal genome dynamics of 39 Klebsiella pneumoniae in a neonatal unit in Blantyre, Malawi

Background: Klebsiella pneumoniae (Kpn) is an important cause of healthcare-associated infections (HAIs). In low- and middle-income countries, HAI due to Kpn disproportionately affects neonates. In this study, we investigated the genomic changes that occurred during long-term circulation of a Kpn sequence type (ST) 39 clone, causing a disproportionate number of infections on the neonatal ward at a tertiary healthcare facility in Malawi in 2017. Methods: We analysed whole-genome sequences of Kpn ST39 collected from Queen Elizabeth Central Hospital over a 20-year period, including the generation of several high-quality hybrid genomes. We compared virulence markers, antibiotic resistance determinants and mobile genetic elements, focusing on variable regions between strains from the outbreak clone in 2017 and genomes from other co-occurring ST39 lineages. Results: We identified eight variable genomic regions that demonstrate the plasticity of Kpn within ST, including the role of bacteriophages in shaping the genome of ST39. Conclusions: The analysed Kpn ST39 lineages have a highly variable genome capable of incorporating large genomic regions during prolonged hospital circulation, which may offer a selective advantage in hospital environments and provide resistance to antimicrobial agents.