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

• Published in: Nature communications Vol. 14; no. 1; p. 7477
• Main Authors: Obolski, Uri, Swarthout, Todd D., Kalizang’oma, Akuzike, Mwalukomo, Thandie S., Chan, Jia Mun, Weight, Caroline M., Brown, Comfort, Cave, Rory, Cornick, Jen, Kamng’ona, Arox Wadson, Msefula, Jacquline, Ercoli, Giuseppe, Brown, Jeremy S., Lourenço, José, Maiden, Martin C., French, Neil, Gupta, Sunetra, Heyderman, Robert S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 59; 631/181/457; 631/208/212; 631/326/325/2482; 631/326/590; 64; 64/60; 692/700/478/174; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial agents; Antimicrobial resistance; Bacteria; Carrier State - epidemiology; Child; Child, Preschool; Drug resistance; Drug Resistance, Bacterial - genetics; Genetics; Genomes; Genotypes; Humanities and Social Sciences; Humans; Infant; Malawi - epidemiology; Metabolism; Mice; multidisciplinary; Nasopharynx; Pneumococcal Infections - epidemiology; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines; Polysaccharides; Population dynamics; Population genetics; Science; Science (multidisciplinary); Serogroup; Serotypes; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - genetics; Vaccines; Virulence; Virulence - genetics; Malawi
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43160-y

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. Pneumococcal vaccination has been shown to promote emergence of non-vaccine S. pneumoniae serotypes. Here, the authors use data from Malawi to investigate whether vaccine introduction also results in changes in metabolic, virulence, and antimicrobial resistance profiles of circulating strains.