Mechanisms, Anti-Quorum-Sensing Actions, and Clinical Trials of Medicinal Plant Bioactive Compounds against Bacteria: A Comprehensive Review

Abstract

Bacterial strains have developed an ability to resist antibiotics via numerous mechanisms. Recently, researchers conducted several studies to identify natural bioactive compounds, particularly secondary metabolites of medicinal plants, such as terpenoids, flavonoids, and phenolic acids, as antibacterial agents. These molecules exert several mechanisms of action at different structural, cellular, and molecular levels, which could make them candidates or lead compounds for developing natural antibiotics. Research findings revealed that these bioactive compounds can inhibit the synthesis of DNA and proteins, block oxidative respiration, increase membrane permeability, and decrease membrane integrity. Furthermore, recent investigations showed that some bacterial strains resist these different mechanisms of antibacterial agents. Researchers demonstrated that this resistance to antibiotics is linked to a microbial cell-to-cell communication system called quorum sensing (QS). Consequently, inhibition of QS or quorum quenching is a promising strategy to not only overcome the resistance problems but also to treat infections. In this respect, various bioactive molecules, including terpenoids, flavonoids, and phenolic acids, exhibit numerous anti-QS mechanisms via the inhibition of auto-inducer releases, sequestration of QS-mediated molecules, and deregulation of QS gene expression. However, clinical applications of these molecules have not been fully covered, which limits their use against infectious diseases. Accordingly, the aim of the present work was to discuss the role of the QS system in bacteria and its involvement in virulence and resistance to antibiotics. In addition, the present review summarizes the most recent and relevant literature pertaining to the anti-quorum sensing of secondary metabolites and its relationship to antibacterial activity.

Antibiofilm Synergistic Activity of Streptomycin in Combination with Thymol-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles against Klebsiella pneumoniae Isolates

“…Thymol interacts with the lipidic bacterial membrane via direct binding with the biomolecules providing strong antimicrobial activity by disrupting the localization of membrane-associated proteins and the permeability of the bacterial cell membranes. Additionally, thymol reduces the biomass of biofilms, prevents adhesion, and destroys the structure of biofilms by modulating the quorum sensing system [ 6 , 7 ]. Thymol was reported to reduce the amount of biofilm of Pseudomonas aeruginosa within the range of 70–77% and 52–75% for Staphylococcus aureus [ 8 ].…”

Research Progress and Hopeful Strategies of Application of Quorum Sensing in Food, Agriculture and Nanomedicine

“…Several natural compounds, mainly terpenoids (eugenol, carvacrol, phytol, linalool, D-limonene and α-pinene), phenolic acids (salicylic acid, rosmarinic acid, cinnamic acid, chlorogenic acid, p-coumaric acid and caffeic acid), flavonoids (epigallocatechin, naringenin, quercetin, naringin, quercetin 4 -O-β-D-glucopyranoside, taxifolin and morin) from plants, as well as enzymes (mainly lactonases, acylases and oxidoreductases) and antibodies (monoclonal antibodies, mAbs RS2-1G9, able to inhibit 3-oxo-C12-AHL-based QS signaling in P. aeruginosa), are reported as QQ agents. They display inhibitory activities through different mechanisms and may act on the synthesis of autoinducers (by deregulating the QS gene expression) or by blocking the cellular receptor [47][48][49]. The development of nanotechnology in medicine has led researchers to design nanostructured materials (nanoparticles and nanocapsules) able to interfere with QS involved in biofilm production and growth.…”

Quorum Sensing Orchestrates Antibiotic Drug Resistance, Biofilm Formation, and Motility in Escherichia coli and Quorum Quenching Activities of Plant-derived Natural Products: A Review

“…Pharmaceutical industries have been pushed to develop new therapeutic agents in recent years due to a paucity of novel antimicrobial agents and the continued increase of antibiotic-resistant bacteria as a result of the abuse and overuse of antibiotics in the treatment of bacterial diseases. 53 Since the discovery of the ability of bacteria to produce autoinducers for bacterial cell-to-cell communication, researchers have used anti-quorum sensing assays to explore for inhibitors to interrupt such bacterial means of communication. 54 Quorum sensing inhibitors (QSI) are a promising alternative…”

“…Zaatar Origanum Essential oils (α-Thujene, α-Pinene, 1-Octen-3-ol, 3-Anti-quorum sensing through inhibition of biofilm formation [53] compactum Octanone, β-Myrcene, α -Terpinene, P-Cymene, D-Limonene, 1,8-Cineole, -Terpinene, Linalool, Terpinen-4-ol, α -Terpineo, thymol, carvacrol, β-Caryophyllene, Caryophyllene oxide) D-limonene Inhibition of biofilm formation in E. coli through the suppression of [65] curli and extracellular polymeric substance (EPS) Decreased swimming and swarming ability of E. coli. Repression of the expression of curli related genes and AI-2 importer genes in E. coli.…”