title: Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection.
abstract: Staphylococcus aureus produces numerous factors that facilitate survival in the human host. S. aureus coagulase (Coa) and von Willebrand factor-binding protein (vWbp) are known to clot plasma through activation of prothrombin and conversion of fibrinogen to fibrin. In addition, S. aureus clumping factor A (ClfA) binds fibrinogen and contributes to platelet aggregation via a fibrinogen- or complement-dependent mechanism. Here, we evaluated the contribution of Coa, vWbp and ClfA to S. aureus pathogenesis in a rabbit model of skin and soft tissue infection. Compared to skin abscesses caused by the Newman wild-type strain, those caused by isogenic coa, vwb, or clfA deletion strains, or a strain deficient in coa and vwb, were significantly smaller following subcutaneous inoculation in rabbits. Unexpectedly, we found that fibrin deposition and abscess capsule formation appear to be independent of S. aureus coagulase activity in the rabbit infection model. Similarities notwithstanding, S. aureus strains deficient in coa and vwb elicited reduced levels of several proinflammatory molecules in human blood in vitro. Although a specific mechanism remains to be determined, we conclude that S. aureus Coa, vWbp and ClfA contribute to abscess formation in rabbits.
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malachowa
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Porter
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Scott
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.affiliation: Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D000038:Abscess / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D003030:Coagulase / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D011817:Rabbits; D018461:Soft Tissue Infections / Q000382:microbiology* / Q000473:pathology; D013207:Staphylococcal Skin Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D016207:Cytokines; D018836:Inflammation Mediators