Role of Fibronectin-Binding Proteins A and B inIn VitroCellular Infections andIn VivoSeptic Infections by Staphylococcus aureus

Abstract

Fibronectin-binding protein A (FnBPA) and FnBPB are important adhesins for Staphylococcus aureus infection. We constructed fnbA and/or fnbB mutant strains from S. aureus SH1000, which possesses intact rsbU, and studied the role of these adhesins in in vitro and in vivo infections. In intravenous infection, all fnb mutants caused a remarkable reduction in the colonization rate in kidneys and the mortality rate of mice. fnbB mutant caused a more severe decrease in body weight than that caused by fnbA mutant. Serum levels of interleukin-6 and nuclear factor B (NF-B) activation in spleen cells were remarkably reduced in fnbA or fnbA fnbB mutant infections; however, there was no significant reduction in fnbB mutant infections. In in vitro cellular infection, FnBPA was shown to be indispensable for adhesion to and internalization by nonprofessional phagocytic cells upon ingestion by inflammatory macrophages and NF-B activation. However, both FnBPs were required for efficient cellular responses. The results showed that FnBPA is more important for in vitro and in vivo infections; however, cooperation between FnBPA and FnBPB is indispensable for the induction of severe infection resulting in septic death.

Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis

“…Indeed, although we analyzed only a small number of animals, which can limit the evaluation of the results, it is interesting the high levels of the proinflammatory cytokines IL-1␤ and IL-6 in plasma following both bolus and continuous-infusion inoculation with L. lactis expressing FnbpA, although bolus inoculation increased cytokine levels earlier than did continuous inoculation. FnbpA was previously shown to induce the production of IL-6 by endothelial cells in vitro (19,35) and to be a major player responsible for both the proinflammatory and the procoagulant endothelium responses in vivo during S. aureus endovascular infections (15,18,36). The increase in the level of IL-1␤ is in line with the findings of previous studies showing that fibronectin induces IL-1␤ gene transcription and increases IL-1␤ protein secretion in vitro (37).…”

Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices

“…We chose to focus on fnbA rather than fnbB because all isolates had fnbA, but only 85% of the CDI isolates possessed the gene for FnBPB (i.e., 15% of the CDI isolates had only fnbA). This distribution is similar to that reported in other studies of clinical isolates, which have found that >70% of isolates have both FnBPA and FnBPB, 20% have only FnBPA, but isolates encoding only FnBPB are rare (∼1%) (24,25). isolates.…”

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic

“…Studies with clinical isolates suggested that strains associated with invasive disease are significantly more likely to have two fnb genes (Peacock et al 2000). Molecular studies have also shown that both FnBPA and FnBPB are required for the establishment of septic infection (Shinji et al 2011). However, in S. aureus that have both homologs, deletion of either gene does not abolish fibronectinbinding capacity of the cell (Greene et al 1995).…”