Glutamyl endopeptidase (Staphylococcus aureus V8) (SspA)

Staphylococcus aureus V8 serine protease, also known as glutamyl endopeptidase (SspA), is a major extracellular virulence factor secreted by S. aureus (UniProt P0C0Q4). It specifically cleaves peptide bonds at the carboxylic side of glutamic acid and, to a lesser extent, aspartic acid residues (MEROPS S21.001). This enzyme plays a critical role in the pathogenesis of staphylococcal infections by degrading host defense proteins, such as immunoglobulins and antimicrobial peptides, thereby facilitating immune evasion (PMID: 15575988). Additionally, SspA is involved in the proteolytic processing of other staphylococcal surface proteins and toxins, contributing to the bacterium's ability to colonize and spread within the host (PMID: 11741840). While not currently the primary target of approved antibiotics, it is considered a promising target for anti-virulence therapy, which aims to disarm the pathogen without exerting the selective pressure that leads to traditional antibiotic resistance (PMID: 24563318). Research into small molecule inhibitors and neutralizing antibodies is ongoing to evaluate the therapeutic potential of blocking SspA activity during systemic and localized infections. The enzyme's high specificity for glutamyl bonds makes it a unique target compared to broader-spectrum proteases.

Other names

V8 proteaseEndoproteinase Glu-CStaphylococcal serine proteaseStaphylococcus aureus V8 proteaseGlutamyl endopeptidase I

Inhibition of serine protease activity to reduce bacterial virulence and enhance host immune clearance.