Obolski, Uri and Swarthout, Todd D. and Kalizang’oma, Akuzike and Mwalukomo, Thandie S. and Chan, Jia Mun and Weight, Caroline M. and Brown, Comfort and Cave, Rory and Cornick, Jen and Kamng’ona, Arox Wadson and Msefula, Jacquline and Ercoli, Giuseppe and Brown, Jeremy S. and Lourenço, José and Maiden, Martin C. and French, Neil and Gupta, Sunetra and Heyderman, Robert S. (2023) The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi. Nature Communications, 14 (1): 7477. ISSN 2041-1723
Full text not available from this repository.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.