Bioactive Quorum Quenchers Antagonizing Pseudomonas Aeruginosa Biofilm

Abstract

Quorum sensing is a generic regulatory mechanism of bacterial communication, allowing the launching of coordinated and unified response of bacteria in a population density-dependent manner to accomplish tasks, difficult to be carried out by an individual bacterium. It is based on secretion of signaling molecules called quorum signals to the environment, and plays a key role in controlling virulence, both in Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa, a Gram-negative bacterium, is an opportunistic pathogen, responsible for acute pulmonary infection and cystic fibrosis, as well as chronic infections, by virtue of natural drug resistance and capability of forming complex biofilms, using a highly complicated quorum sensing signaling mechanism, which is difficult to be cleared by antibiotic therapy. The quorum sensing system constitutes N-acyl homoserine lactone (AHL)-dependent regulatory circuits, modulated by a non-AHL related signal molecule, along with numerous regulators at the transcriptional and post-transcriptional level. Therefore, inhibition of quorum signals by using certain bioactive compounds, called quorum quenchers, especially phytochemicals, provides safe and effective remedial measure to eradicate infection caused by antibiotic-resistant P. aeruginosa. The promising quenchers make the biofilm more susceptible to antibiotics, thereby reducing virulence and mortality. They are either naturally found or can be synthetically designed through chemical engineering. Many of them are enzymes, degrading signaling molecules or impeding cellular signaling cascades. These quenchers are therefore attractive targets as next generation novel drugs that can be used in therapeutics to overcome the problem of antibiotic resistance issue of many bacteria due to careless and rampant use of increasing dosage of antibiotics.