Host chemokines bind to Staphylococcus aureus and stimulate protein A release.
There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.
Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sunny C
SC
Yung
David
D
Parenti
Philip M
PM
Murphy
D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002473:Cell Wall / Q000276:immunology* / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism
C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D013205:Staphylococcal Protein A; D037521:Virulence Factors