Methicillin-resistant Staphylococcus pseudintermedius synthesizes deoxyadenosine to cause persistent infection.
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Authors
Bünsow, DorotheaTantawy, Eshraq
Ostermeier, Tjorven
Bähre, Heike
Garbe, Annette
Larsen, Jesper
Winstel, Volker
Issue Date
2021-03-29
Metadata
Show full item recordAbstract
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an emerging zoonotic pathogen of canine origin that causes an array of fatal diseases, including bacteremia and endocarditis. Despite large-scale genome sequencing projects have gained substantial insights into the genomic landscape of MRSP, current knowledge on virulence determinants that contribute to S. pseudintermedius pathogenesis during human or canine infection is very limited. Using a panel of genetically engineered MRSP variants and a mouse abscess model, we here identified the major secreted nuclease of S. pseudintermedius designated NucB and adenosine synthase A (AdsA) as two synergistically acting enzymes required for MRSP pathogenesis. Similar to Staphylococcus aureus, S. pseudintermedius requires nuclease secretion along with the activity of AdsA to degrade mammalian DNA for subsequent biosynthesis of cytotoxic deoxyadenosine. In this manner, S. pseudintermedius selectively kills macrophages during abscess formation thereby antagonizing crucial host immune cell responses. Ultimately, bioinformatics analyses revealed that NucB and AdsA are widespread in the global S. pseudintermedius population. Together, these data suggest that S. pseudintermedius deploys the canonical Nuc/AdsA pathway to persist during invasive disease and may aid in the development of new therapeutic strategies to combat infections caused by MRSP.Citation
Virulence. 2021 Dec;12(1):989-1002. doi: 10.1080/21505594.2021.1903691.Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
Taylor & FrancisJournal
VirulencePubMed ID
33779509Type
ArticleLanguage
enEISSN
2150-5608ae974a485f413a2113503eed53cd6c53
10.1080/21505594.2021.1903691
Scopus Count
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- Creative Commons
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