Influence of Streptococcus pneumoniae Within-Strain Population Diversity on Virulence and Pathogenesis

Jacques, Laura C, Green, Angharad E, Barton, Thomas E, Baltazar, Murielle ORCID: 0000-0002-1972-2308, Aleksandrowicz, Julia, Xu, Rong ORCID: 0009-0005-8895-0303, Trochu, Erwan, Kadioglu, Aras ORCID: 0000-0003-1137-6321 and Neill, Daniel R (2023) Influence of Streptococcus pneumoniae Within-Strain Population Diversity on Virulence and Pathogenesis MICROBIOLOGY SPECTRUM, 11 (1). e0310322-. ISSN 2165-0497, 2165-0497

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Abstract

The short generation time of many bacterial pathogens allows the accumulation of de novo mutations during routine culture procedures used for the preparation and propagation of bacterial stocks. Taking the major human pathogen Streptococcus pneumoniae as an example, we sought to determine the influence of standard laboratory handling of microbes on within-strain genetic diversity and explore how these changes influence virulence characteristics and experimental outcomes. A single culture of S. pneumoniae D39 grown overnight resulted in the enrichment of previously rare genotypes present in bacterial freezer stocks and the introduction of new variation to the bacterial population through the acquisition of mutations. A comparison of D39 stocks from different laboratories demonstrated how changes in bacterial population structure taking place during individual culture events can cumulatively lead to fixed, divergent change that profoundly alters virulence characteristics. The passage of D39 through mouse models of infection, a process used to standardize virulence, resulted in the enrichment of high-fitness genotypes that were originally rare (,2% frequency) in D39 culture collection stocks and the loss of previously dominant genotypes. In the most striking example, the selection of a,2%-frequency genotype carrying a mutation in sdhB, a gene thought to be essential for the establishment of lung infection, was associated with enhanced systemic virulence. Three separately passaged D39 cultures originating from the same frozen stocks showed considerable genetic divergence despite comparable virulence.

Item Type:	Article
Uncontrolled Keywords:	Streptococcus pneumoniae, evolution, infectious disease, population genetics, virulence
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	06 Jan 2023 12:34
Last Modified:	16 Jun 2026 10:20
DOI:	10.1128/spectrum.03103-22
Open Access URL:	https://doi.org/10.1128/spectrum.03103-22
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166839
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