Characterization of Virulence Factors of Staphylococcus aureus: Novel Function of Known Virulence Factors That Are Implicated in Activation of Airway Epithelial Proinflammatory Response

Abstract

Airway epithelial cells play a major role in initiating inflammation in response to bacterial pathogens. S. aureus is an important pathogen associated with activation of diverse types of infection characterized by inflammation dominated by polymorphonuclear leukocytes. This bacterium frequently causes lung infection, which is attributed to virulence factors. Many of virulence determinants associated with S. aureus-mediated lung infection have been known for several years. In this paper, we discuss recent advances in our understanding of known virulence factors implicated in pneumonia. We anticipate that better understanding of novel functions of known virulence factors could open the way to regulate inflammatory reactions of the epithelium and to develop effective strategies to treat S. aureus-induced airway diseases.

Figure 1

Role of SpA in TNFR1 regulation. (a) SpA is recognized by TNFR1 and the signaling cascade is initiated through the adaptor proteins TRADD/RIP/TRAF2, which subsequently activate MAPK kinases (p38 and JNK 1/2) and induce translocation of transcription factors AP-1 and NF-κB into the nucleus. Activation of AP-1 and NF-κB leads to transcription of genes encoding proinflammatory cytokines and chemokines. (b) SpA through interaction with EGFR and activation of c-Src-Erk1/2 stimulates the activity of TACE (ADAM-17), which cleaves and releases TNFR1 from the airway surface. TNFR1 is then available to neutralize free SpA and TNF-α ligands. AP-1, activator protein 1; ATF-2, activating transcription factor 2; EGFR, epidermal growth factor receptor; NF-κB, nuclear factor κB; RIP, receptor-interacting protein; TACE, tumor necrosis factor-α-converting enzyme; TNFR1, tumor necrosis factor receptor 1; TRADD, tumor necrosis factor receptor- (TNFR-) associated death domain; TRAF2, tumor necrosis factor receptor-associated factor 2.