Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin.
A549 Cells
Animals
Autolysis
Bacteremia
/ microbiology
Bacterial Proteins
/ metabolism
Bacterial Toxins
Cell Survival
Disease Models, Animal
Epithelial Cells
/ microbiology
Female
Humans
Lung
/ microbiology
Mice
Mice, Inbred BALB C
Nasopharynx
/ microbiology
Pneumococcal Infections
/ microbiology
Serogroup
Streptococcus pneumoniae
/ metabolism
Streptolysins
/ metabolism
Virulence
Virulence Factors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
22
01
2019
accepted:
23
03
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
5
8
2020
Statut:
epublish
Résumé
Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.
Identifiants
pubmed: 32312961
doi: 10.1038/s41467-020-15751-6
pii: 10.1038/s41467-020-15751-6
pmc: PMC7170840
doi:
Substances chimiques
Bacterial Proteins
0
Bacterial Toxins
0
Streptolysins
0
Virulence Factors
0
plY protein, Streptococcus pneumoniae
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1892Subventions
Organisme : Medical Research Council
ID : MR/N002679/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011284/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204457/Z/16/Z
Pays : United Kingdom
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