Title:Small Molecules Modulating AHL-based Quorum Sensing to Attenuate Bacteria Virulence and Biofilms as Promising Antimicrobial Drugs
VOLUME: 21 ISSUE: 3
Author(s):Y. Wang and S. Ma
Affiliation:Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
Keywords:AHLs, antimicrobial drugs, bacterial virulence, biofilms, inhibitors, quorum sensing.
Abstract:Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. Yet new
antibiotics are currently being developed at a much slower pace than our growing need for such drugs. Instead of focusing
on conventional therapeutics that target in vitro bacterial viability, an alternative therapy is to target virulence factors and
biofilms. Such anti-virulence strategies have attracted more and more attention rencently, for it would add both supplement
and diversity to our current antimicrobial library. This approach has several potential advantages including imposing
less evolutionary pressure on the development of antibiotic resistance, increasing the antibacterial targets and preserving
the host endogenous microbiome. Quorum sensing is an intercellular communication process in bacterial communities,
which can regulate coordinated expression of virulence factors and biofilms. N-Acyl homoserine lactones (AHLs) are
autoinducers generated by a variety of Gram-negative bacteria. These signals combining with their cognate LuxR-type receptors
trigger the expression of virulence genes. In this critical review, we summarize various structual types of small
molecules targeting AHL-based quorum sensing to attenuate bacteria virulence factors and biofilms.