Virulence of Pseudomonas aeruginosa exposed to carvacrol: alterations of the Quorum sensing at enzymatic and gene levels

Abstract

The main goal of this study was to evaluate the inhibition of Pseudomonas aeruginosa virulence factors and Quorum Sensing during exposure to carvacrol. P. aeruginosa (ATCC 10154) was exposed to carvacrol determining changes in biofilm development, motility, acyl-homoserine lactones (AHL) synthesis and relative expression of lasI/lasR. Docking analysis was used to determinate interactions between carvacrol with LasI and LasR proteins. P. aeruginosa produced 60% lower AHLs when exposed to carvacrol (1.9 mM) compared to control, without affecting cellular viability, indicating a reduction on the LasI synthase activity. AHL-C12, C6, and C4 were detected and related to biofilm development, motility, and pyocyanin production, respectively. The presence of carvacrol reduced the expression of lasR, without affecting lasI gen. Moreover, computational docking showed interactions of carvacrol with amino acids in the active site pocket of LasI (−5.6 kcal mol −1 ) and within the binding pocket of LasR (−6.7 kcal mol −1 ) of P. aeruginosa. These results demonstrated that virulence of P. aeruginosa was reduced by carvacrol, by inhibiting LasI activity with the concomitant reduction on the expression of lasR, biofilm and swarming motility. This study provides relevant information about the effect of carvacrol against quorum sensing to inhibit virulence factors of P. aeruginosa at enzymatic and gene levels. These findings can contribute to the development of natural anti-QS products, which can affect pathogenesis.

In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections

“…The severity and extent of diseases caused by these pathogens are also amplified when the pathogens are organized in biofilms, the most relevant structures responsible for persistent infections, that constitute a major challenge for microbiologists and clinicians. A biofilm is a microorganisms' community that produces an extracellular matrix to attach itself to biotic or abiotic surfaces, embedded in an aqueous matrix of extracellular polymeric substances (EPS) [8]. Bacteria growing in biofilms are commonly even more resistant to antimicrobial agents and are protected from the host immune response, thus increasing chronic infections that are particularly difficult to nurse [9,10].…”

Quorum Sensing Inhibiting Activity of Cefoperazone and Its Metallic Derivatives on Pseudomonas aeruginosa

“…The basic residues, Lys150, Arg154, Arg161, His165, Lys167, and Arg172 form a highly positive charged patch on the LasI surface ( Gould et al., 2004 ). Likewise, carvacrol interacts with LasI synthase Arg104 residue through Van der Waals forces and occupies the LasR binding site pocket at Asp73 residue, with subsequent elimination of the expression of virulence factors in P. aeruginosa ( Tapia-Rodriguez et al., 2019 ).…”

Aporphinoid alkaloids inhibit biofilm formation of Yersinia enterocolitica isolated from sausages

“…Similar results have been observed with other natural products. Tapia‐Rodriguez et al (2019), reported a potential anti‐virulence mode of action of carvacrol against P. aeruginosa . After demonstrating a reduction in biofilm formation without altering the planktonic culture, they observed a reduction on the lasR expression, AHLs and related virulence factor production without reduction in lasI expression.…”