title: Paradigm shift in discovering next-generation anti-infective agents: targeting quorum sensing, c-di-GMP signaling and biofilm formation in bacteria with small molecules.
abstract: Small molecules that can attenuate bacterial toxin production or biofilm formation have the potential to solve the bacteria resistance problem. Although several molecules, which inhibit bacterial cell-to-cell communication (quorum sensing), biofilm formation and toxin production, have been discovered, there is a paucity of US FDA-approved drugs that target these processes. Here, we review the current understanding of quorum sensing in important pathogens such as Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus and provide examples of experimental molecules that can inhibit both known and unknown targets in bacterial virulence factor production and biofilm formation. Structural data for protein targets that are involved in both quorum sensing and cyclic diguanylic acid signaling are needed to aid the development of molecules with drug-like properties in order to target bacterial virulence factors production and biofilm formation.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA. hsintim@umd.edu
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
authors.forename: Jacqueline A I
authors.initials: JA
authors.lastname: Smith
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.forename: Shizuka
authors.initials: S
authors.lastname: Nakayama
authors.forename: Lei
authors.initials: L
authors.lastname: Yan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D018407:Bacterial Physiological Phenomena; D018441:Biofilms / Q000187:drug effects*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D053038:Quorum Sensing / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP