Zap Protease Biochemistry - Proteus mirabilis

We have identified two metalloproteases secreted by Proteus mirabilis, referred to as ZapA and ZapE, that may be important for the survival of the bacteria. ZapA is an important virulence factor of P. mirabilis, as we have shown by comparing the survival of ZapA^- mutants with the isogenic wild type strain during urinary tract infection (UTI). The function of ZapE is not known, however its amino acid sequence suggests that ZapE may function either as a cytolysin or hemolysin. While it is known that ZapA has the ability to degrade host immunoglobulins, the dramatic attenuation of virulence in strains lacking ZapA suggests that ZapA and ZapE may have a broader spectrum of activity associated with virulence. This project tests the hypothesis that the roles of ZapA and ZapE in UTI extend beyond cleavage of IgA and IgG, and that the principal substrates of these metalloproteases are other proteins found in the urinary tract, specifically epithelial cell membrane proteins.