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

Obolski, Uri; Swarthout, Todd D; Kalizang’oma, Akuzike; Mwalukomo, Thandie S; Chan, Jia Mun; Weight, Caroline M; Brown, Comfort; ... Heyderman, Robert S; + view all (2023) The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi. Nature Communications , 14 (1) , Article 7477. 10.1038/s41467-023-43160-y. Green open access

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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.

Type: Article
Title: The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-023-43160-y
Publisher version: https://doi.org/10.1038/s41467-023-43160-y
Language: English
Additional information: © 2023 Springer Nature Limited. his article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Bacterial genetics, Epidemiology, Genomics, Population genetics, Vaccines
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10181818
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