Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity

Panagiotou, Stavros ORCID: 0000-0001-9972-5068, Chaguza, Chrispin ORCID: 0000-0002-2108-1757, Yahya, Reham, Audshasai, Teerawit, Baltazar, Murielle ORCID: 0000-0002-1972-2308, Ressel, Lorenzo ORCID: 0000-0002-6614-1223, Khandaker, Shadia, Alsahag, Mansoor, Mitchell, Tim J, Prudhomme, Marc
et al (show 2 more authors) (2020) Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity. SCIENTIFIC REPORTS, 10 (1). 17313-.

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Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.

Item Type: Article
Uncontrolled Keywords: Animals, Humans, Mice, Streptococcus pneumoniae, Hemolysis, Bacterial Proteins, Streptolysins, Virulence, Female, Serogroup
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2020 10:03
Last Modified: 18 Jan 2023 23:25
DOI: 10.1038/s41598-020-73454-w
Open Access URL: https://doi.org/10.1038/s41598-020-73454-w
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3105287