Abstract
Bacterial quorum sensing (QS) is a cell-cell communication system that regulates several bacterial mechanisms, including the production of virulence factors and biofilm formation. Thus, targeting microbial QS is seen as a plausible alternative strategy to antibiotics, with potentiality to combat multidrug-resistant pathogens. Many phytochemicals with QS interference activity are currently being explored. Herein, an extract and a compound of bioinspired origin were tested for their ability to inhibit biofilm formation and interfere with the expression of QS-related genes in Pseudomonas aeruginosa and Staphylococcus aureus. The extract, a carboxypyranoanthocyanins red wine extract (carboxypyrano-ant extract), and the pure compound, carboxypyranocyanidin-3-O-glucoside (carboxypyCy-3-glc), did not cause a visible effect on the biofilm formation of the P. aeruginosa biofilms; however, both significantly affected the formation of biofilms by the S. aureus strains, as attested by the crystal violet assay and fluorescence microscopy. Both the extract and the pure compound significantly interfered with the expression of several QS-related genes in the P. aeruginosa and S. aureus biofilms, as per reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results. Indeed, it was possible to conclude that these molecules interfere with QS at distinct stages and in a strain-specific manner. An extract with anti-QS properties could be advantageous because it is easily obtained and could have broad, antimicrobial therapeutic applications if included in topical formulations.
Highlights
Antimicrobial resistance (AMR) is one of the most concerning global public health threats of today, resulting in a significant increase in mortality and morbidity due to bacterial infections that were once treatable but are life threatening, entailing huge economic costs [1,2].Over the last years, researchers have been striving to find and develop new antibiotics to effectively treat multidrug-resistant bacterial infections, those caused by the so-called priority pathogens, which are bacterial species with critical, high, and medium antibiotic resistance [3]
The aim of this study was to explore a carboxypyranoanthocyanins extract obtained from the reaction of red wine anthocyanins with pyruvic acid, and a pure carboxypyranocyanidin-3-O-glucoside, which have previously shown to effectively hamper the biofilm formation of P. aeruginosa ATCC 27853 and S. aureus ATCC 29213 [24], for their: (i) effect in the biofilm formation of the P. aeruginosa and S. aureus multidrug-resistant (MDR) isolates; (ii) ability to interfere with the expression of the quorum sensing (QS)-related genes of the
It was described that some compounds present in red wine, such as other flavonoids like flavonols derivatives (myricetinO-(O-galloyl)arabinoside, myricetin-3-O-arabinoside, quercetin 3-methoxyhexoside and quercetin 3-O-glucuronide tentatively identified) present in our carboxypyrano-ant extract, have anti-virulence activity and affect biofilm formation, and, they could contribute to the inhibition of biofilm formation observed in the presence of the carboxypyrano-ant extract [19,38]
Summary
Antimicrobial resistance (AMR) is one of the most concerning global public health threats of today, resulting in a significant increase in mortality and morbidity due to bacterial infections that were once treatable but are life threatening, entailing huge economic costs [1,2].Over the last years, researchers have been striving to find and develop new antibiotics to effectively treat multidrug-resistant bacterial infections, those caused by the so-called priority pathogens, which are bacterial species with critical, high, and medium antibiotic resistance [3]. A recently explored strategy regards the use of anti-virulence agents, known as drugs that can block the virulence factors of the pathogen, impairing its ability to cause infection [4,6]. These drugs can, in theory, control bacterial infections not by killing the pathogen, but by affecting other pathways and mechanisms, such as their communication system, known as quorum sensing (QS). Inhibiting QS could reduce virulence factor production and biofilm formation, increasing the sensibility of the pathogen to antimicrobials and allowing the host immune system to tackle the infection more [6,12,13].
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