Methicillin-resistant Staphylococcus pseudintermedius synthesizes deoxyadenosine to cause persistent infection

Autor:	Jesper Larsen, Volker Winstel, Dorothea Bünsow, Annette Garbe, Tjorven Ostermeier, Eshraq Tantawy, Heike Bähre
Přispěvatelé:	HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Rok vydání:	2021
Předmět:	Methicillin-Resistant Staphylococcus aureus Microbiology (medical) Staphylococcus pseudintermedius Staphylococcus Immunology Population abscess Virulence Infectious and parasitic diseases RC109-216 Biology medicine.disease_cause Microbiology Pathogenesis Mice 03 medical and health sciences Dogs Immune system medicine Animals Secretion Dog Diseases nuclease education deoxyadenosine 030304 developmental biology 0303 health sciences education.field_of_study Deoxyadenosines 030306 microbiology adenosine synthase A Staphylococcal Infections biology.organism_classification medicine.disease Anti-Bacterial Agents Infectious Diseases Staphylococcus aureus Bacteremia Methicillin Resistance Persistent Infection Parasitology Research Article Research Paper
Zdroj:	Virulence article-version (VoR) Version of Record Virulence, Vol 12, Iss 1, Pp 989-1002 (2021) United States
ISSN:	2150-5608 2150-5594
Popis:	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.
Databáze:	OpenAIRE
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