Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis

Abstract

The pathogenic role of staphylococcal coagulase and clumping factor was investigated in the rat model of endocarditis. The coagulase-producing and clumping factor-producing parent strain Staphylococcus aureus Newman and a series of mutants defective in either coagulase, clumping factor, or both were tested for their ability (i) to attach in vitro to either rat fibrinogen or platelet-fibrin clots and (ii) to produce endocarditis in rats with catheter-induced aortic vegetations. In vitro, the clumping factor-defective mutants were up to 100 times less able than the wild type strain to attach to fibrinogen and also significantly less adherent than the parents to platelet-fibrin clots. Coagulase-defective mutants, in contrast, were not altered in their in vitro adherence phenotype. The rate of in vivo infection was inoculum dependent. Clumping factor-defective mutants produced ca. 50% less endocarditis than the parent organisms when injected at inoculum sizes infecting, respectively, 40 and 80% (ID 40 and ID 80 , respectively) of rats with the wild-type strain. This was a trend at the ID 40 but was statistically significant at the ID 80 (P < 0.05). Coagulase-defective bacteria were not affected in their infectivity. Complementation of a clumping factor-defective mutant with a copy of the wild-type clumping factor gene restored both its in vitro adherence and its in vivo infectivity. These results show that clumping factor plays a specific role in the pathogenesis of S. aureus endocarditis. Nevertheless, the rate of endocarditis with clumping factor-defective mutants increased with larger inocula, indicating the contribution of additional pathogenic determinants in the infective process.

A molecular epidemiological study of methicillin-resistantStaphylococcienvironmental contamination in railway stations and coach stations in Guangzhou of China

“…After incubating at 37°C for 24 h, the swabs were plated onto mannitol salt agar plates and incubated for another 24 h. We isolated one isolate from one sample. Isolates that can ferment mannitol and tolerate 7Á5% concentration of sodium chloride were identified as Staphylococci if they were grape-like clusters and Gram-positive under microscope and positive for catalase test (Hill 1959 (Edmiston et al 1989;Moreillon et al 1995). Staphylococci isolates that were positive for the mecA gene and/or resistant to cefoxitin were labelled as methicillin-resistant Staphylococci.…”

Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments

“…A failure to recover mutants with defects in attachment protein genes such as clumping factor, protein A and adhesins might also be attributable to inoculum effects. Accordingly, clumping factor-defective mutants have been demonstrated to show increased in vivo endocarditis infection rates that correlate with increases in inoculum dosage (Moreillon et al, 1995).…”

New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans

“…S. aureus strains express ClfA, a conserved surface protein, initially described for its ability to promote the precipitation (clumping reaction) of staphylococci in vitro via its binding to the soluble fibrinogen (McAdow et al, 2011). ClfA has been clearly demonstrated to be a major virulence factor in many animal models, including animal models of endocarditis and septic arthritis (Hu et al, 2009;Josefsson et al, 2001;Moreillon et al, 1995). However, the extents to which ClfAenhanced virulence is mediated by its interaction with fibrinogen (McAdow et al, 2011), complement regulator factor I (Hair et al, 2008(Hair et al, , 2010 or other serum proteins remain unresolved.…”