Developing anti-virulence chemotherapies by exploiting the diversity of microbial quorum sensing systems

Quorum sensing is a process of chemical communication that adjusts the genetic expression of certain important biological functions in a cell-density- dependent manner. Quorum sensing (QS) regulates important bacterial behaviors, such as production of virulence factors, formation of biofilm, and antibiotic resistance, via signaling molecules called autoinducers (AIs). Gram-negative bacteria typically use N-acyl homoserine lactones (AHLs) and S-adenosyl methionine (SAM) molecules as signaling molecules for communication with neighboring cells, while Gram-positive bacteria use oligopeptides for the same purpose. Autoinducer-2 (AI-2) is used as a signaling molecule by both Gram-negative and Gram-positive bacteria. These QS molecules are often involved in the expression of pathogenicity in different bacterial species. Because of the rapid emergence and dissemination of drug-resistant pathogens worldwide, antivirulence chemotherapies may be potential alternatives to the use of antibiotics, which kill bacteria but allow the emergence of resistance. Recently, successful strategies, employed for inhibition/ manipulation of QS signaling, has brought real excitement for identifying novel advances to combat these life-threatening pathogens. This review highlights the QS systems used by Gram-negative and Gram-positive bacterial species and discusses promising QS inhibitor (QSI) molecules that may aid in designing novel antimicrobial therapeutics. Utilization of different QS components in the design and development of novel biotechnological products, such as biosensors, engineered microbial consortia, and anticancer molecules, is also addressed.