Polymorphisms in Fibronectin Binding Proteins A and B among Staphylococcus aureus Bloodstream Isolates Are Not Associated with Arthroplasty Infection

Abstract

BackgroundNonsynonymous single nucleotide polymorphisms (SNPs) in fibronectin binding protein A (fnbA) of Staphylococcus aureus are associated with cardiac device infections. However, the role of fnbA SNPs in S. aureus arthroplasty infection is unknown.MethodsBloodstream S. aureus isolates from a derivation cohort of patients at a single U.S. medical center with S. aureus bacteremia (SAB) and prosthetic hip or knee arthroplasties that were infected (PJI, n = 27) or uninfected (PJU, n = 43) underwent sequencing of fnbA and fnbB. A validation cohort of S. aureus bloodstream PJI (n = 12) and PJU (n = 58) isolates from Germany also underwent fnbA and fnbB sequencing.ResultsOverall, none of the individual fnbA or fnbB SNPs were significantly associated with the PJI or PJU clinical groups within the derivation cohort. Similarly, none of the individual fnbA or fnbB SNPs were associated with PJI or PJU when the analysis was restricted to patients with either early SAB (i.e., bacteremia occurring <1 year after placement or manipulation of prostheses) or late SAB (i.e., bacteremia >1 year after placement or manipulation of prostheses).ConclusionsIn contrast to cardiac device infections, there is no association between nonsynonymous SNPs in fnbA or fnbB of bloodstream S. aureus isolates and arthroplasty infection. These results suggest that initial steps leading to S. aureus infection of cardiovascular and orthopedic prostheses may arise by distinct processes.

The microbiological characteristics ofStaphylococcus aureusisolated from patients with native valve infective endocarditis

“…While similar observations have been reported in other studies [29], a recent study of prosthetic joint infection with S. aureus found no polymorphic or amino acid sequence differences in the fnbp gene [11]. Here, we found that SNPs in previously described loci including E652D, H782Q, K786N, H818Q, T826N, and S839N were not significantly different between the IE and non-IE groups.…”

“…This suggests that the ability of S. aureus to attach to undamaged endothelial cells could be the key mechanism in S. aureus IE. This observation has led many to speculate that pathogenassociated factors may play more a central role in the development of IE than previously thought [10,11]. Staphylococcus aureus expresses a wide range of virulence factors, including microsomal surface component recognizing adhesive matrix molecule family (MSCRAMM) and numerous secretory toxins [12].…”

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

“…However, a similar role for fibronectin binding was not found for hematogenous PJI in humans (45). To identify potential pathogenic factors that contributed to the hematogenous orthopedic implant infection in our mouse model, we investigated S. aureus AT and ClfA because they are involved in biofilm formation in vitro (35,36) and in human synovial fluid specimens ex vivo (38) and have been implicated in septic arthritis (39, 40) and primary orthopedic implant infections in mice and humans (37,41).…”

Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin-binding protein A affect bond strength and fibronectin conformation

“…These experiments were performed on the wild-type peptide and each of the double mutant peptides. We focused on the double rather than single mutants because multiple polymorphisms have been linked to disease in humans (12,14,15,47). Supplemental Table S2 shows these k off values for NTD-Fn.…”