Abstract
Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections that can often evolve to severe infections. The rise of antibiotic-resistant strains has driven the search for novel therapies to replace the use or act as adjuvants of antibiotics. In this context, plant-derived compounds have been widely investigated. Cuminaldehyde is suggested as the major antimicrobial compound of the cumin seed essential oil. However, this effect is not fully understood. Herein, we investigated the in silico and in vitro activities of cuminaldehyde, as well as its ability to potentiate ciprofloxacin effects against S. aureus and E. coli. In silico analyses were performed by using different computational tools. The PASS online and SwissADME programmes were used for the prediction of biological activities and oral bioavailability of cuminaldehyde. For analysis of the possible toxic effects and the theoretical pharmacokinetic parameters of the compound, the Osiris, SwissADME and PROTOX programmes were used. Estimations of cuminaldehyde gastrointestinal absorption, blood brain barrier permeability and skin permeation by using SwissADME; and drug likeness and score by using Osiris, were also evaluated The in vitro antimicrobial effects of cuminaldehyde were determined by using microdilution, biofilm formation and time-kill assays. In silico analysis indicated that cuminaldehyde may act as an antimicrobial and as a membrane permeability enhancer. It was suggested to be highly absorbable by the gastrointestinal tract and likely to cross the blood brain barrier. Also, irritative and harmful effects were predicted for cuminaldehyde if swallowed at its LD50. Good oral bioavailability and drug score were also found for this compound. Cuminaldehyde presented antimicrobial and anti-biofilm effects against S. aureus and E. coli.. When co-incubated with ciprofloxacin, it enhanced the antibiotic antimicrobial and anti-biofilm actions. We suggest that cuminaldehyde may be useful as an adjuvant therapy to ciprofloxacin in S. aureus and E. coli-induced infections.
Highlights
Bacteria such as Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections [1,2,3,4]
The unrestricted and widespread use of antibiotics in the last decades resulted in a rise of multidrug-resistant strains of both E. coli and S. aureus, reducing the chances of a successful treatment of infections caused by these microorganisms
Studies with the essential oil of C. cyminum seeds indicated its antimicrobial potential against a series of bacteria including S. aureus and E. coli [20,21,22,23,24,25,26,27]
Summary
Bacteria such as Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections [1,2,3,4] Both bacteria are frequently detected in patients with indwelling urinary tract devices [1, 5,6,7]. Reports indicate S. aureus is responsible for 21 to 36 cases of bacteremia per 100,000 habitants per year [10, 11] with mortality rates varying from 30 to 70% [12]. The management of such infections mostly relies on antibiotic therapy, with patient survival and recovery largely depending on treatment timing and efficacy. Plant-derived compounds have been widely investigated as antimicrobials and adjuvants to antibiotic therapy [16, 17]
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