Chemical probes of quorum sensing: from compound development to biological discovery.
Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a method of cell-cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues.
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA.
Michael A
MA
Welsh
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA blackwell@chem.wisc.edu.
Helen E
HE
Blackwell
D054742:Acyl-Butyrolactones / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D018441:Biofilms / Q000254:growth & development; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*; D053038:Quorum Sensing / Q000187:drug effects* / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D037521:Virulence Factors / Q000096:biosynthesis
D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; C085427:LuxI protein, Bacteria; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; C064778:LuxR autoinducer binding proteins
LuxR-type receptor; Pseudomonas aeruginosa; acylated homoserine lactone; antivirulence; chemical biology; quorum sensing