Inhibition of Urease Enzyme Production and some Other Virulence Factors Expression in Proteus mirabilis by N-Acetyl Cysteine and Dipropyl Disulphide

Proteus mirabilis is one of the important pathogens that colonize the urinary tract and catheters resulting in various complications, such as blockage of the catheters and the formation of infective stones. Purpose: In this study we evaluated the effect of N-acetyl cysteine (NAC) and dipropyl disulphide on some virulence factors expressed by a Proteus mirabilis strain isolated from a catheterized patient. Methods: Antibacterial activity of both compounds was determined by broth microdilution method. Their effect on different types of motility was determined by LB medium with variable agar content and sub-MIC of each drug. Their effect on adherence and mature biofilms was tested by tissue culture plate assay. Inhibitory effect on urease production was determined and supported by molecular docking studies. Results: The minimum inhibitory concentration (MIC) of NAC and dipropyl disulphide was 25 mM and 100 mM, respectively. Both compounds decreased the swarming ability and biofilm formation of the tested isolate in a dosedependent manner. NAC had higher urease inhibitory activity (IC50 249 +/-0.05 mM) than that shown by dipropyl disulphide (IC50 10+/-0.2 mM). Results were supported by molecular docking studies which showed that NAC and dipropyl disulphide interacted with urease enzyme with binding free energy of -4.8 and -8.528 kcal/mol, respectively. Docking studies showed that both compounds interacted with Ni ion and several amino acids (His-138, Gly-279, Cysteine-321, Met-366 and His-322) which are essential for the enzyme activity. Conclusion: NAC and dipropyl disulphide could be used in the control of P. mirabilis urinary tract infections.