Quinolones: from antibiotics to autoinducers

• Published in: FEMS microbiology reviews Vol. 35; no. 2; pp. 247 - 274
• Main Authors: Heeb, Stephan, Fletcher, Matthew P, Chhabra, Siri Ram, Diggle, Stephen P, Williams, Paul, Cámara, Miguel
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Blackwell; Oxford University Press
• Subjects: Anti-Bacterial Agents - metabolism; Antibiotics; Anticancer properties; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Biosynthesis; Burkholderia; Chelating agents; Cytochrome; Cytochrome bc1; Cytochromes; Drug development; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Bacterial; Hydroxyquinoline; Iron; Metabolites; Microbiology; Microorganisms; Miscellaneous; Population density; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - metabolism; Quinine; quinoline; quinolone; Quinolones; Quinolones - metabolism; quorum sensing; Review; Virulence; quinolone; quinoline; quorum sensing; virulence; Pseudomonadales; Antibiotic; Virulence; Bacteria; Pseudomonadaceae; Quorum sensing; Review; Burkholderia; Pseudomonas
• ISSN: 0168-6445; 1574-6976; 1574-6976
• DOI: 10.1111/j.1574-6976.2010.00247.x

Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc₁ complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression.