Unraveling the Impact of Secreted Proteases on Hypervirulence in <i>Staphylococcus aureus</i>
Brittney D. Gimza, Jessica K. Jackson, Andrew M. Frey, Bridget G. Budny, Dale Chaput, Devon Rizzo, Lindsey N. Shaw
Abstract
, who specifically and selectively modulate virulence factor stability. In our previous work we demonstrated that deletion of all 10 secreted proteases results in hypervirulence, since virulence factors exist unchecked, leading to overly aggressive infections. Here, using a combinatorial collection of protease mutants, we reveal that deletion of aureolysin and staphopain A is necessary and sufficient to elicit hypervirulence. Using proteomic techniques, we identify the collection of virulence factors that accumulate in hypervirulent protease mutants, and demonstrate that a well-known toxin (LukA) and an entirely novel secreted element (SAUSA300_0964) are the leading contributors to deadly infections observed in protease-lacking strains.