Understanding protease-mediated host-pathogen interactions in <i>Proteus mirabilis</i>

These cytokines and receptors are heavily involved in pro-inflammatory responses and therefore these data corroborate previous literature that demonstrate the immuno-evasive properties of ZapA. However, it was also found that ZapA proteolytically processes pro-IL-1ß into its mature active form, IL-1ß, another pro-inflammatory cytokine. Furthermore, it was found that ZapA degrades flagellin monomers; this may be particularly useful during swarming motility, in which <i>P. mirabilis</i> cells become hyperflagellated, to avoid Toll-like receptor 5 (TLR5)-mediated recognition.

The <i>N</i>-alpha mercaptoamide dipeptide inhibitor, ME-YV, was included in these experiments and shown to prevent ZapA-mediated effects, validating the efficacy of ZapA as a target for the action of anti-virulence agents. Multiplex substrate profiling by mass spectrometry (MSP-MS) of ZapA and other <i>Proteus </i>spp. proteases has potentially facilitated the development of unique, highly specific substrates which could be applied as part of a point-of-care (POC) assay to rapidly diagnose urinary tract infections, demonstrating the efficacy of proteases as biomarkers.<br><br>