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

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 D. Swarthout, Ken Malisita, Arox W. Kamng’ona, Robert S. Heyderman, Stephen D. Bentley, Brenda A. Kwambana-Adams, Chrispin Chaguza and Kondwani C. Jambo ()
Additional contact information
Lusako L. Sibale: Malawi-Liverpool-Wellcome Programme
Stephanie W. Lo: Wellcome Genome Campus, Hinxton
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
Akuzike Kalizang’oma: Malawi-Liverpool-Wellcome Programme
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
Chrispin Chaguza: Wellcome Genome Campus, Hinxton
Kondwani C. Jambo: Malawi-Liverpool-Wellcome Programme

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63974-2

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