The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

Uri Obolski (), Todd D. Swarthout, Akuzike Kalizang’oma, Thandie S. Mwalukomo, Jia Mun Chan, Caroline M. Weight, Comfort Brown, Rory Cave, Jen Cornick, Arox Wadson Kamng’ona, Jacquline Msefula, Giuseppe Ercoli, Jeremy S. Brown, José Lourenço, Martin C. Maiden, Neil French, Sunetra Gupta and Robert S. Heyderman ()
Additional contact information
Uri Obolski: Tel Aviv University
Todd D. Swarthout: Malawi Liverpool Wellcome Programme
Akuzike Kalizang’oma: Malawi Liverpool Wellcome Programme
Thandie S. Mwalukomo: Kamuzu University of Health Sciences
Jia Mun Chan: University College London
Caroline M. Weight: University College London
Comfort Brown: Malawi Liverpool Wellcome Programme
Rory Cave: University College London
Jen Cornick: Malawi Liverpool Wellcome Programme
Arox Wadson Kamng’ona: Kamuzu University of Health Sciences
Jacquline Msefula: Kamuzu University of Health Sciences
Giuseppe Ercoli: University College London
Jeremy S. Brown: University College London
José Lourenço: University of Oxford
Martin C. Maiden: University of Oxford
Neil French: University of Liverpool
Sunetra Gupta: University of Oxford
Robert S. Heyderman: Malawi Liverpool Wellcome Programme

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into “Metabolic genotypes” (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.

Date: 2023
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DOI: 10.1038/s41467-023-43160-y

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