Repurposing carvacrol, cinnamaldehyde, and eugenol as potential anti-quorum sensing agents against uropathogenic Escherichia coli isolates in Alexandria, Egypt

Abstract

Background Urinary tract infections represent one of the most frequent hospital and community-acquired infections with uropathogenic Escherichia coli (UPEC) being the main causative agent. The global increase in the emergence of multidrug-resistant (MDR) UPEC necessitates exploring novel approaches. Repurposing natural products as anti-quorum sensing (QS) agents to impede bacterial virulence is gaining momentum nowadays. Hence, this study investigates the anti-QS potentials of carvacrol, cinnamaldehyde, and eugenol against E. coli isolated from urine cultures of Egyptian patients. Results Antibiotic susceptibility testing was performed for 67 E. coli isolates and 94% of the isolates showed MDR phenotype. The usp gene was detected using PCR and accordingly, 45% of the isolates were categorized as UPEC. Phytochemicals, at their sub-inhibitory concentrations, inhibited the swimming and twitching motilities of UPEC isolates, with eugenol showing the highest inhibitory effect. The agents hindered the biofilm-forming ability of the tested isolates, at two temperature sets, 37 and 30 °C, where eugenol succeeded in significantly inhibiting the biofilm formation by > 50% at both investigated temperatures, as compared with untreated controls. The phytochemicals were shown to downregulate the expression of the QS gene (luxS) and critical genes related to motility, asserting their anti-QS potential. Further, the combinatory activity of the phytoproducts with five antibiotics was assessed by checkerboard assay. The addition of the phytoproducts significantly reduced the minimum inhibitory concentrations of the antibiotics and generated several synergistic or partially synergistic combinations, some of which have not been previously explored. Conclusions Overall, carvacrol, cinnamaldehyde, and eugenol could be repurposed as potential anti-QS agents, which preferentially reduce the QS-based communication and attenuate the cascades of gene expression, thus decreasing the production of virulence factors in UPEC, and eventually, subsiding their pathogenicity. Furthermore, the synergistic combinations of these agents with antibiotics might provide a new perspective to circumvent the side effects brought about by high antibiotic doses, thereby paving the way for overcoming antibiotic resistance.

Bioactive Compounds from Plant Origin as Natural Antimicrobial Agents for the Treatment of Wound Infections

“…There was also a decrease in bacterial biofilm formation. In addition, the synergistic effect of CNA in combination with tigecycline on UPEC E. coli has been demonstrated [202]. Another study showed the high effectiveness of the CNA combination with silver nanoparticles (the MIC value = 0.008-0.016 mg•mL −1 ) against MDR E. coli strain EAEC (Enteroaggregative E. coli).…”

“…The molecular analysis identified a decrease in the expression of the luxS gene, which is important in quorum sensing. The reduced expression of fimA (adhesion fimbria) and fliC (flagella) genes was observed [202].…”

“…Increased expression of the AI-2 factor [168] Reduction of bacterial exopolysaccharide formation [179] Direct inhibition of ESP protein [180] Decreased level of QS involved genes encoding: hemolysins, proteases, elastases, alginate, pyrocyanin, and ramnolipid expression [190][191][192] Inhibition of exopolysaccharide synthesis [190] Inhibition of icaA and icaD gene expression [173] Inhibition of gene-encoding PIA glucosamine polymer expression [173] Inhibition of fsrB, fsrC, luxS, and gelE gene expression [179] Inhibition of: csuA, csuE, bfmS, bfmR, ompa, bap, abal genes expression [188] Reduction of the intracellular concentration of bis-(3 ′ -5 ′ )-cyclic dimeric GMP [213] Reduction in the formation of acyl homoserine lactones [191] Inhibition of luxS, fimA, and fliC gene expression [202] Ellagic acid…”