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Temporal genome dynamics of ST39 Klebsiella pneumoniae in a neonatal unit in Blantyre, Malawi

Zuza, A. M.; Pearse, O.; Domman, D. B.; Dyson, Z. A.; Kawaza, K.; Musicha, P.; Feasey, N. A.; Heinz, E.

2025-11-09 infectious diseases
10.1101/2025.11.06.25339690 medRxiv
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BackgroundKlebsiella pneumoniae (Kpn) is an important cause of healthcare-associated infections (HAI). In low and middle-income countries, HAI due to Kpn disproportionally affects neonates. In this study, we investigated the genomic changes that occurred during long-term circulation of a Kpn ST39 clone, causing a disproportionate number of infections on the neonatal ward at a tertiary healthcare facility in Malawi in 2017. MethodsWe analyzed whole genome sequences of Klebsiella pneumoniae ST39 collected from Queen Elizabeth Central Hospital over a 20-year period, including 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 to genomes from other co-occurring ST39 lineages. ResultsWe identified eight variable genomic regions that demonstrate the plasticity of Kpn within-ST, including the role of bacteriophages in shaping the genome of ST39. ConclusionsThe analyzed Klebsiella pneumoniae 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. Data summaryAll sequencing data is available in BioProject PRJEB102175; detailed accession numbers are provided in Table S1. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

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