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 acetamide 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 promising antivirulence agent against the P. mirabilis uropathogens and as potential therapy for treatment of urinary tract infections (UTIs).
Highlights
Urinary tract infections (UTI) are the major cause of healthcare associated infections accounting for 40% of all hospital acquired infections
Competition between microorganisms living in the environment drives them to produce a wide range of secondary metabolites to aid their survival in the presence of other microbes [7], they become a source for potential antivirulent agents
MO, USA), except L-tryptophan (Trp), indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and tryptamine (TAM), which were the products of Acros Organics (Morris Plains, NJ, USA), and indole-3-pyruvic acid (IPyA), which was purchased from Santa Cruz Biotechnology (Dallas, TX, USA)
Summary
Urinary tract infections (UTI) are the major cause of healthcare associated infections accounting for 40% of all hospital acquired infections. Catheter associated urinary tract infections (CAUTI) represent approximately 80% of Healthcare associated UTIs [1]. Bacteria that belong to the family Enterobacteriaceae are the most frequent causative agent of UTIs. Clinically, Proteus mirabilis is the most common cause of complicated urinary tract infections, in patients suffering from long-term catherization. Proteus mirabilis is the most common cause of complicated urinary tract infections, in patients suffering from long-term catherization These infections are complicated by catheter encrustation and blockage resulting from the ability of this bacterium to produce crystalline biofilm [2]. P. mirabilis is an opportunistic pathogen, which is widely spread in the environment, mainly found in water, soil, and the gastrointestinal tracts of humans and animals
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