Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Scientific reports - 10(2020), 1 vom: 14. Okt., Seite 17313 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Panagiotou, Stavros [VerfasserIn] |
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| Links: |
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| Themen: |
Bacterial Proteins |
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| Anmerkungen: |
Date Completed 09.04.2021 Date Revised 29.03.2022 published: Electronic ErratumIn: Sci Rep. 2021 Mar 17;11(1):6658. - PMID 33731755 Citation Status MEDLINE |
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| doi: |
10.1038/s41598-020-73454-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316266493 |
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| 500 | |a ErratumIn: Sci Rep. 2021 Mar 17;11(1):6658. - PMID 33731755 | ||
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| 520 | |a 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 | ||
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| 700 | 1 | |a Baltazar, Murielle |e verfasserin |4 aut | |
| 700 | 1 | |a Ressel, Lorenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Khandaker, Shadia |e verfasserin |4 aut | |
| 700 | 1 | |a Alsahag, Mansoor |e verfasserin |4 aut | |
| 700 | 1 | |a Mitchell, Tim J |e verfasserin |4 aut | |
| 700 | 1 | |a Prudhomme, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Kadioglu, Aras |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Marie |e verfasserin |4 aut | |
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