Abstract:
Proteus mirabilis is a frequent cause of catheter associated urinary tract infections (CAUTIs).
Several virulence factors contribute to its pathogenesis, but swarming motility, biofilm formation,
and urease activity are considered the hallmarks. The increased prevalence in antibiotic resistance
among uropathogens is alarming and requires searching for new treatment alternatives. With this in
mind, our study aims to investigate antivirulence activity of indole derivatives against multidrug
resistant P. mirabilis isolates. Ethyl acetate (EtOAc) extracts from Enterobacter sp. (rhizobacterium),
isolated from Egyptian soil samples were tested for their ability to antagonize the virulence capacity
and biofilm activity of P. mirabilis uropathogens. Extracts of two Enterobacter sp. isolates (coded
Zch127 and Cbg70) showed the highest antivirulence activities against P. mirabilis. The two promising
rhizobacteria Zch127 and Cbg70 were isolated from soil surrounding: Cucurbita pepo (Zucchini) and
Brassica oleracea var. capitata L. (Cabbage), respectively. Sub-minimum inhibitory concentrations
(Sub-MICs) of the two extracts showed potent antibiofilm activity with significant biofilm reduction
of ten P. mirabilis clinical isolates (p-value < 0.05) in a dose-dependent manner. Interestingly, the
Zch127 extract showed anti-urease, anti-swarming and anti-swimming activity against the tested
strains. Indole derivatives identified represented key components of indole pyruvate, indole ac-
etamide pathways; involved in the synthesis of indole acetic acid. Additional compounds for indole
acetonitrile pathway were detected in the Zch127 extract which showed higher antivirulence activity.
Accordingly, the findings of the current study model the feasibility of using these extracts as promis-
ing antivirulence agent against the P. mirabilis uropathogens and as potential therapy for treatment of
urinary tract infections (UTIs).
