Screening strategies for quorum sensing inhibitors in combating bacterial infections

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Catechol-derived Inhibitors against Quorum Sensing from Retiboletus kauffmanii

[Objectives]This study aimed to screen anti-quorum sensing(QS)activity from the constituent of Retiboletus kauffmanii fruit body.[Methods]Chromatographic technology was used to isolate compounds,while well diffusion assay was applied to screen anti-quorum sensing activity.[Results]12 phenolic compounds were purified from extracts,three catechol-derived compounds at sub-inhibitory concentrations were found to inhibit the production of violacein in Chromobacterium violaceum for the first time.[Conclusions]Three catechol analogs isolated from R.kauffmanii fruit body extract were indicated as quorum sensing inhibitors against C.violaceum.

Degradation of N-Acyl Homoserine Lactone Quorum Sensing Signals by Bacillus thuringiensis AHL Lactonase

Bacterial cells rely on signaling molecules to communicate with others from the same species and induce certain genes in a process known as quorum sensing (QS). A common molecule is N-acyl homoserine lactone (AHL) which is responsible for the expression of virulence and other factors that allow the organisms to compete in a given environment. On the other hand, other bacteria produce certain enzymes such as AHL-lactonase that break down AHL molecules and prevent gene expression of these factors. The aim of this work was to examine the level of degradation of AHL molecules by AHL-lactonase in 62 Bacillus thuringiensis (Bt) strains isolated from Middle Tennessee, Mississippi, and Alabama. N-hexanoyl-homoserine lactone (C6-HSL) and N-3-oxo-hexanoyl homoserine lactone (3-oxo-C6-HSL), which cause Chromobacterium violaceum (CV026) to produce a purple pigment were tested at different concentrations to view the Bt lactonase activity. In addition, PCR was used to test for the presence of the lactonase gene. The results showed that among the 62 Bt strains, there were 58 that possessed the AHL-lactonase (aiiA) gene and 48 strains were able to degrade C6-HSL. At high concentrations of AHL, only 13 strains were able to completely degrade C6-HSL. In addition, degradation of 3-oxo-C6-HSL was weak compared to C6-HSL. The results also revealed that AHL lactonase was thermostable, and it was concluded that the level of degradation varies in Bt strains. Only 13 of the strains studied have potent inhibitory activity against C6-HSL, which may be good to be used in field applications to control agricultural pest.

Bioaugmentation and quorum sensing disruption as solutions to increase nitrate removal in sequencing batch reactors treating nitrate-rich wastewater

Bioaugmentation of denitrifying bacteria can serve as a promising technique to improve nutrient removal during wastewater treatment. While denitrification inhibition by bacterial quorum sensing(QS) in Pseudomonas aeruginosa has been indicated, the application of bacterial QS disruption to improve nitrate removal from wastewater has not been investigated. In this study, the effect of bioaugmentation of P. aeruginosa SD-1 on nitrate removal in sequencing batch reactors that treat nitrate rich wastewater was assessed. Additionally, the potential of a quorum sensing inhibitor(QSI) to improve denitrification following bacterial bioaugmentation was evaluated. Curcumin, a natural plant extract, was used as a QSI. The chemical oxygen demand(COD) and initial nitrate concentration of the influent were 700 ±20 mg/L and 200 ±10 mg/L respectively, and their respective concentrations in the effluent were 56.9 ±3.2 mg/L and 9.0 ±3.2 mg/L. Thus, the results revealed that bioaugmentation of P. aeruginosa SD-1 resulted in an increased nitrate removal to 82% ±1%. Further, nitrate was almost completely removed following the addition of the QSI, and activities of nitrate reductase and nitrite reductase increased by 88% ±2% and 74% ±2% respectively. The nitrogen mass balance indicated that aerobic denitrification was employed as the main pathway for nitrogen removal in the reactors. The results imply that bioaugmentation and modulation of QS in denitrifying bacteria, through the use of a QSI, can enhance nitrate removal during wastewater treatment.