Potassium 2-methoxy-4-vinylphenolate: a novel hit exhibiting quorum-sensing inhibition in<i>Pseudomonas aeruginosa via</i>LasIR/RhlIR circuitry

Shah, Mayank D.; Kharkar, Prashant S.; Sahu, Niteshkumar U.; Peerzada, Zoya; Desai, Krutika

doi:10.1039/c9ra06612h

Cited by 9 publications

(6 citation statements)

References 58 publications

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“…The data corroborate our qRT-PCR data, which were also significant to show a complete blockage of virulence so as to prevent the colonization and dissemination of bacteria to persist infection. A derivative of 2-methoxy-4-vinylphenol has already been reported to have an inhibitory activity against LasIR/RhIIR circuit of Pseudomonas aeruginosa (Shah et al, 2019). Interestingly, hexahydro-3-(phenylmethyl)pyrrolo[1,2-a]pyrazine-1,4-dione, also known as cyclo D-phenyalanyl-L-prolyl [Cyclo(Phe-Pro)], has been reported to attenuate the expression of genes associated with virulence in V. cholerae.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Anti-infectives From Mangrove-Derived Micromonospora sp. RMA46 to Combat Vibrio cholerae Pathogenesis

et al. 2020

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Vibrio cholerae, the etiological agent of cholera, employs quorum sensing (QS) pathways to control the expression of virulence factors, including the production of cholera toxin and biofilm formation. Acquired antibiotic resistance in V. cholerae draws attention to the development of novel therapeutics that counteract virulence, rather than the viability of the pathogen. In this context, we explored the anti-infective potential of rare marine Actinobacteria (RMA) from a mangrove ecosystem. Here, we report the effects of Micromonospora sp. RMA46 against V. cholerae in vitro. The RMA46 organic extract was non-bactericidal to V. cholerae cells and non-cytotoxic to macrophage RAW264.7 cell lines. RMA46 inhibited the formation of V. cholerae biofilms and downregulated the QS global switches LuxO and HapR, as well as other virulence genes including ct, tcp, and hapA. In silico molecular docking simulation of RMA46 ethyl acetate extract with LuxO and HapR revealed that 2-methoxy-4-vinylphenol and hexahydro-3-(phenylmethyl)-pyrrolo[1,2-a]pyrazine-1,4-dione could interact with the active sites of LuxO and HapR and potentially inhibit them. This study highlights Micromonospora sp. RMA46 as a potential source of anti-infectives against V. cholerae.

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Section: Discussionmentioning

confidence: 99%

Exploration of Anti-infectives From Mangrove-Derived Micromonospora sp. RMA46 to Combat Vibrio cholerae Pathogenesis

et al. 2020

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“…Meanwhile, it can bind to another QS receptor RhlR. Potassium 2-methoxy-4-vinylphenolate 4 5 ( Figure 14 a) has a partially similar structure to that of 6-gingerol, and it was found to target P. aeruginosa las and rhl circuitry and to inhibit biofilm formation along with various virulence factors such as LasA protease, LasB elastase and pyocyanin [ 98 ]. The potential active compound 4 6 ( Figure 14 a) isolated from the extract of Delftia tsuruhatensis SJ01 was identified as 1,2-benzenedicarboxylic acid diisooctylester, having a similar structure with AHL.…”

Section: Inhibitors Acting On Multiple Qs Systemsmentioning

confidence: 99%

The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

Shen

Wang

et al. 2022

Marine Drugs

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The survival selection pressure caused by antibiotic-mediated bactericidal and bacteriostatic activity is one of the important inducements for bacteria to develop drug resistance. Bacteria gain drug resistance through spontaneous mutation so as to achieve the goals of survival and reproduction. Quorum sensing (QS) is an intercellular communication system based on cell density that can regulate bacterial virulence and biofilm formation. The secretion of more than 30 virulence factors of P. aeruginosa is controlled by QS, and the formation and diffusion of biofilm is an important mechanism causing the multidrug resistance of P. aeruginosa, which is also closely related to the QS system. There are three main QS systems in P. aeruginosa: las system, rhl system, and pqs system. Quorum-sensing inhibitors (QSIs) can reduce the toxicity of bacteria without affecting the growth and enhance the sensitivity of bacterial biofilms to antibiotic treatment. These characteristics make QSIs a popular topic for research and development in the field of anti-infection. This paper reviews the research progress of the P. aeruginosa quorum-sensing system and QSIs, targeting three QS systems, which will provide help for the future research and development of novel quorum-sensing inhibitors.

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“…Another report by Shah et al [249] found a synthetic compound potassium 2-methoxy-4-vinylphenolate to be the most powerful P. aeruginosa quorum-sensing inhibitor that targets LasIR/RhlIR circuits and inhibits the formation of biofilm, production of virulenceassociated factors like LasA protease, pyocyanin, LasB elastase, and motilities in bacteria. Recently, a study by Nain et al [250] utilized energy-optimized pharmacophore coupled virtual screening to discover QS inhibitors for LasR of P. aeruginosa based on hydrogen bond networking and further exploited the stability of the binding complexes through a dynamics simulation study.…”

Section: In Silico Approach To Control P Aeruginosa Biofilmsmentioning

confidence: 99%

Pseudomonas aeruginosa Biofilm Formation and Its Control

et al. 2021

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Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be necessary to avoid inappropriate treatment strategies. Hence, the search for other alternative strategies as effective biofilm treatment options has become a growing area of research. The current review aims to give an overview of the mechanisms governing biofilm formation and the different strategies employed so far in the control of biofilm infections caused by P. aeruginosa. Moreover, this review can also help researchers to search for new antibiofilm agents to tackle the effect of biofilm infections that are currently imprudent to conventional antibiotics.

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Potassium 2-methoxy-4-vinylphenolate: a novel hit exhibiting quorum-sensing inhibition inPseudomonas aeruginosa viaLasIR/RhlIR circuitry

Abstract: Effect of potassium 2-methoxy-4-vinylphenolate on quorum sensing in Pseudomonas aeruginosa.

Cited by 9 publications

References 58 publications

Exploration of Anti-infectives From Mangrove-Derived Micromonospora sp. RMA46 to Combat Vibrio cholerae Pathogenesis

Exploration of Anti-infectives From Mangrove-Derived Micromonospora sp. RMA46 to Combat Vibrio cholerae Pathogenesis

The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

Pseudomonas aeruginosa Biofilm Formation and Its Control

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