title: Staphylococcus aureus synthesizes adenosine to escape host immune responses.
abstract: Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. We examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall-anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen, and adenosine synthesis also enabled escape of Bacillus anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vilasack
authors.initials: V
authors.lastname: Thammavongsa
authors.forename: Justin W
authors.initials: JW
authors.lastname: Kern
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000038:Abscess / Q000382:microbiology / Q000473:pathology; D000241:Adenosine / Q000096:biosynthesis* / Q000097:blood; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001408:Bacillus anthracis / Q000166:cytology / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D002455:Cell Division; D002473:Cell Wall / Q000201:enzymology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006868:Hydrolysis; D007108:Immune Tolerance; D007109:Immunity / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D000241:Adenosine