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Within-host genetic diversity of pneumococcal serotype 3 during one-year prolonged carriage in a healthy adult

Author

Listed:
  • Lusako L. Sibale

    (Malawi-Liverpool-Wellcome Programme
    Liverpool School of Tropical Medicine
    Wellcome Genome Campus, Hinxton)

  • Stephanie W. Lo

    (Wellcome Genome Campus, Hinxton
    University of Bath
    University College London)

  • Newton Kalata

    (Malawi-Liverpool-Wellcome Programme)

  • Tinashe K. Nyazika

    (University of Wolverhampton)

  • Ndaona Mitole

    (Malawi-Liverpool-Wellcome Programme)

  • Victoria Dyster

    (Wellcome Genome Campus, Hinxton)

  • Alice Kusakala

    (Malawi-Liverpool-Wellcome Programme)

  • Mercy Khwiya

    (Malawi-Liverpool-Wellcome Programme)

  • Gift Sagawa

    (Malawi-Liverpool-Wellcome Programme)

  • Joseph A. Phiri

    (Malawi-Liverpool-Wellcome Programme
    Liverpool School of Tropical Medicine)

  • Akuzike Kalizang’oma

    (Malawi-Liverpool-Wellcome Programme
    Liverpool School of Tropical Medicine
    University College London)

  • Todd D. Swarthout

    (University College London)

  • Ken Malisita

    (Lighthouse-Queen Elizabeth Hospital and Gateway Health Centre)

  • Arox W. Kamng’ona

    (Kamuzu University of Health Sciences)

  • Robert S. Heyderman

    (University College London)

  • Stephen D. Bentley

    (Wellcome Genome Campus, Hinxton)

  • Brenda A. Kwambana-Adams

    (Malawi-Liverpool-Wellcome Programme
    Liverpool School of Tropical Medicine
    University College London)

  • Chrispin Chaguza

    (Wellcome Genome Campus, Hinxton
    University College London
    Yale University
    St. Jude Children’s Research Hospital)

  • Kondwani C. Jambo

    (Malawi-Liverpool-Wellcome Programme
    Liverpool School of Tropical Medicine
    Kamuzu University of Health Sciences)

Abstract

Streptococcus pneumoniae adapts within hosts through genetic variation and genome plasticity, facilitating persistence under antibiotic and immune pressures. Here, we investigated a prolonged pneumococcal carriage episode (>337 days) in a healthy, HIV-uninfected adult in Malawi. Whole-genome sequencing of single-colony isolates and plate sweep samples confirmed persistent colonisation by a multidrug-resistant serotype 3 strain with a distinct sequence type (GPSC10-ST18362), which maintained stable predominance despite transient acquisition of other serotypes. The sequentially sampled isolates showed 2 to 11 single-nucleotide polymorphism differences, no evidence of recombination, and modest gene loss involving mobile genetic elements. The total genome size decreased from 2.06 Mb to 2.03 Mb across isolates. Intrahost single-nucleotide variants were identified in genes related to metabolism, stress response, and DNA repair, but showed no consistent signatures of positive selection. Capsular locus analysis revealed deletions consistent with GPSC10-related vaccine-escape profiles. These findings highlight the capacity of GPSC10-ST18362 to persist asymptomatically for months with limited within-host genomic diversity.

Suggested Citation

  • Lusako L. Sibale & Stephanie W. Lo & Newton Kalata & Tinashe K. Nyazika & Ndaona Mitole & Victoria Dyster & Alice Kusakala & Mercy Khwiya & Gift Sagawa & Joseph A. Phiri & Akuzike Kalizang’oma & Todd , 2025. "Within-host genetic diversity of pneumococcal serotype 3 during one-year prolonged carriage in a healthy adult," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63974-2
    DOI: 10.1038/s41467-025-63974-2
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    References listed on IDEAS

    as
    1. 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.
    2. Deus Thindwa & Nicole Wolter & Amy Pinsent & Maimuna Carrim & John Ojal & Stefano Tempia & Jocelyn Moyes & Meredith McMorrow & Jackie Kleynhans & Anne von Gottberg & Neil French & PHIRST group & Chery, 2021. "Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016–2018: A hidden Markov modelling study," PLOS Computational Biology, Public Library of Science, vol. 17(12), pages 1-19, December.
    3. repec:plo:pone00:0038271 is not listed on IDEAS
    4. 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.
    5. Chrispin Chaguza & Madikay Senghore & Ebrima Bojang & Rebecca A. Gladstone & Stephanie W. Lo & Peggy-Estelle Tientcheu & Rowan E. Bancroft & Archibald Worwui & Ebenezer Foster-Nyarko & Fatima Ceesay &, 2020. "Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    6. repec:plo:pmed00:1000081 is not listed on IDEAS
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