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

Author

Listed:
  • Uri Obolski

    (Tel Aviv University
    Tel Aviv University)

  • Todd D. Swarthout

    (Malawi Liverpool Wellcome Programme
    University College London
    University Medical Center Utrecht)

  • Akuzike Kalizang’oma

    (Malawi Liverpool Wellcome Programme
    University College London)

  • Thandie S. Mwalukomo

    (Kamuzu University of Health Sciences)

  • Jia Mun Chan

    (University College London)

  • Caroline M. Weight

    (University College London
    Lancaster University
    Lancaster University)

  • Comfort Brown

    (Malawi Liverpool Wellcome Programme)

  • Rory Cave

    (University College London)

  • Jen Cornick

    (Malawi Liverpool Wellcome Programme
    University of Liverpool)

  • 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
    Biomedical Research Centre)

  • Martin C. Maiden

    (University of Oxford)

  • Neil French

    (University of Liverpool)

  • Sunetra Gupta

    (University of Oxford)

  • Robert S. Heyderman

    (Malawi Liverpool Wellcome Programme
    University College London)

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.

Suggested Citation

  • 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 , 2023. "The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43160-y
    DOI: 10.1038/s41467-023-43160-y
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    References listed on IDEAS

    as
    1. Todd D. Swarthout & Claudio Fronterre & José Lourenço & Uri Obolski & Andrea Gori & Naor Bar-Zeev & Dean Everett & Arox W. Kamng’ona & Thandie S. Mwalukomo & Andrew A. Mataya & Charles Mwansambo & Mar, 2020. "High residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Nicholas J. Croucher & Paul G. Coupland & Abbie E. Stevenson & Alanna Callendrello & Stephen D. Bentley & William P. Hanage, 2014. "Diversification of bacterial genome content through distinct mechanisms over different timescales," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    3. Caroline M. Weight & Cristina Venturini & Sherin Pojar & Simon P. Jochems & Jesús Reiné & Elissavet Nikolaou & Carla Solórzano & Mahdad Noursadeghi & Jeremy S. Brown & Daniela M. Ferreira & Robert S. , 2019. "Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Nicholas J Croucher & Lisa Kagedan & Claudette M Thompson & Julian Parkhill & Stephen D Bentley & Jonathan A Finkelstein & Marc Lipsitch & William P Hanage, 2015. "Selective and Genetic Constraints on Pneumococcal Serotype Switching," PLOS Genetics, Public Library of Science, vol. 11(3), pages 1-21, March.
    5. Evelyn Balsells & Laurence Guillot & Harish Nair & Moe H Kyaw, 2017. "Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-20, May.
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