Document Type
Article
Publication Date
2016
Keywords
fibrinogen, coagulase, fibrin, mice, vaccines, molecule, killing, pathogenic organism
Digital Object Identifier (DOI)
https://doi.org/10.1084/jem.20150074
Abstract
Host immunity against bacteria typically involves antibodies that recognize the microbial surface and promote phagocytic killing. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of lethal bloodstream infection; however, vaccines and antibody therapeutics targeting staphylococcal surface molecules have thus far failed to achieve clinical efficacy. S. aureus secretes coagulase (Coa), which activates host prothrombin and generates fibrin fibrils that protect the pathogen against phagocytosis by immune cells. Because of negative selection, the coding sequence for the prothrombin-binding D1-D2 domain is highly variable and does not elicit cross-protective immune responses. The R domain, tandem repeats of a 27-residue peptide that bind fibrinogen, is conserved at the C terminus of all Coa molecules, but its functional significance is not known. We show here that the R domain enables bloodstream infections by directing fibrinogen to the staphylococcal surface, generating a protective fibrin shield that inhibits phagocytosis. The fibrin shield can be marked with R-specific antibodies, which trigger phagocytic killing of staphylococci and protect mice against lethal bloodstream infections caused by a broad spectrum of MRSA isolates. These findings emphasize the critical role of coagulase in staphylococcal escape from opsonophagocytic killing and as a protective antigen for S. aureus vaccines.
Rights Information
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Experimental Medicine, v. 213, issue 3, p. 293-301
Scholar Commons Citation
Thomer, Lena; Emolo, Carla; Thammavongsa, Vilasack; Kim, Hwan Keun; McAdow, Molly E.; Yu, Wenqi; Kieffer, Matthew; Schneewind, Olaf; and Missiakas, Dominique, "Antibodies against a Secreted Product of Staphylococcus aureus Trigger Phagocytic Killing" (2016). Molecular Biosciences Faculty Publications. 135.
https://digitalcommons.usf.edu/bcm_facpub/135
Supplemental Material
