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; Kondwani C. Jambo

doi:10.1038/s41467-025-63974-2

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, Kondwani C. Jambo

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	8920
Number of pages	1
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-63974-2
Publication status	Published - 7 Oct 2025

Data Availability Statement

The whole-genome sequences (reads) were deposited in the National Center for Biotechnology Information (NCBI) under project code PRJNA1137437, with individual accessions given in Supplementary Data 2 for single-colony-derived sequences and Supplementary Data 3 for plate sweep-derived sequences. Annotated minority variants are available in Supplementary Data 1. Supplementary figures and tables are available in the Supplementary Information. The data generated in this study have been deposited in the Figshare repository. All processed data are openly available in Figshare https://figshare.com/s/f5a679547ae62e0a01c6 and Source data are provided with this paper.

Funding

This work was supported by the National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens through an award to K.C.J. and R.S.H. [16/136/46]. K.C.J. was also supported by an MRC African Research Leader award [MR/T008822/1], and R.S.H. is a NIHR senior investigator. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK government. A Wellcome Strategic award number 206545/Z/17/Z supports MLW.

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Sibale, L. L., Lo, S. W., Kalata, N., Nyazika, T. K., Mitole, N., Dyster, V., Kusakala, A., Khwiya, M., Sagawa, G., Phiri, J. A., Kalizang'oma, A., Swarthout, T. D., Malisita, K., Kamng'ona, A. W., Heyderman, R. S., Bentley, S. D., Kwambana-Adams, B. A., Chaguza, C., & Jambo, K. C. (2025). Within-host genetic diversity of pneumococcal serotype 3 during one-year prolonged carriage in a healthy adult. Nature Communications, 16(1), Article 8920. https://doi.org/10.1038/s41467-025-63974-2

Sibale, LL, Lo, SW, Kalata, N, Nyazika, TK, Mitole, N, Dyster, V, Kusakala, A, Khwiya, M, Sagawa, G, Phiri, JA, Kalizang'oma, A, Swarthout, TD, Malisita, K, Kamng'ona, AW, Heyderman, RS, Bentley, SD, Kwambana-Adams, BA, Chaguza, C & Jambo, KC 2025, 'Within-host genetic diversity of pneumococcal serotype 3 during one-year prolonged carriage in a healthy adult', Nature Communications, vol. 16, no. 1, 8920. https://doi.org/10.1038/s41467-025-63974-2

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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.",

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AU - Phiri, Joseph A.

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AU - Heyderman, Robert S.

AU - Bentley, Stephen D.

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AB - 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.

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

Abstract

Data Availability Statement

Funding

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UN SDGs

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