Clumping factor B is an important virulence factor during Staphylococcus aureus skin infection and a promising vaccine target

Staphylococcus aureus expresses a number of cell wall-anchored proteins that mediate adhesion and invasion of host cells and tissues and promote immune evasion, consequently contributing to the virulence of this organism. The cell wall-anchored protein clumping factor B (ClfB) has previously been shown to facilitate S. aureus nasal colonization through high affinity interactions with the cornified envelope in the anterior nares. However, the role of ClfB during skin and soft tissue infection (SSTI) has never been investigated. This study reveals a novel role for ClfB during SSTIs. ClfB is crucial in determining the abscess structure and bacterial burden early in infection and this is dependent upon a specific interaction with the ligand loricrin which is expressed within the abscess tissue. Targeting ClfB using a model vaccine that induced both protective humoral and cellular responses, leads to protection during S. aureus skin infection. This study therefore identifies ClfB as an important antigen for future SSTI vaccines. Author summary Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs), the treatment of which is becoming increasingly difficult due to antibiotic resistance. An anti-S. aureus vaccine offers a potential solution, but a better understanding of how S. aureus causes pathology during SSTI is required to identify effective vaccine targets. Here, we identify an important virulence determinant during S. aureus SSTI. Clumping factor B (ClfB), a surface protein expressed by S. aureus is shown to promote skin abscess formation by binding to the host protein loricrin. Targeting ClfB using a model vaccine conferred significant protection during S. aureus SSTI. In this study, we uncover an entirely novel mechanism by which S. aureus forms abscesses during skin infection, identifying an important therapeutic target for treating S. aureus SSTI.