Differential Expression and Roles of Staphylococcus aureus Virulence Determinants during Colonization and Disease

Abstract

Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens.

Investigation on the effect of known potent S. aureus NorA efflux pump inhibitors on the staphylococcal biofilm formation

“…In S. aureus, a well-known pathogen growing in biolm and causing tremendous chronic infections in patients with prostheses or cystic brosis, 28 the most expressed EP is NorA encoded by the norA gene. 29 The NorA pump is a cytoplasmic membrane protein belonging to the Major Facilitator Superfamily and it uses a proton motive force to energize the transport of antimicrobial agents (e.g.…”

Derepression of SaPIbov1 Is Independent of φNM1 Type 2 dUTPase Activity and Is Inhibited by dUTP and dUMP

“…People colonized with S. aureus are more susceptible to infection, which occurs when there is a breach of the skin or mucosal membrane [3, 5–7]. Pathogenic S. aureus isolates have an up-regulation of virulence genes compared to the commensal strains [8, 9]. …”

Host-derived fatty acids activate type VII secretion inStaphylococcus aureus

“…One reason for this apparent paradox is the diverse arsenal of virulence factors that clinically relevant S. aureus strains, such as USA300, specifically deploy upon bacterial penetration of dermal and mucosal barriers. For example, transcription of a key virulence factor, Panton-Valentine leukocidin (LukF-PV), is decreased during nasal colonization but is substantially up-regulated during blood and cardiac infection (2). Some virulence genes enhance bacterial survival in blood through a variety of mechanisms, including the scavenging of scarce nutrients, as well as by evading and neutralizing the host immune response.…”