title: Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa.
abstract: The development of new approaches for the treatment of antimicrobial-resistant infections is an urgent public health priority. The Pseudomonas aeruginosa pathogen, in particular, is a leading source of infection in hospital settings, with few available treatment options. In the context of an effort to develop antivirulence strategies to combat bacterial infection, we identified a series of highly effective small molecules that inhibit the production of pyocyanin, a redox-active virulence factor produced by P. aeruginosa. Interestingly, these new antagonists appear to suppress P. aeruginosa virulence factor production through a pathway that is independent of LasR and RhlR.
authors.affiliation: Department of Chemistry and ‡Department of Molecular Biology, Princeton University , Washington Road, Princeton, New Jersey 08544, United States.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Miller
authors.forename: Colleen T
authors.initials: CT
authors.lastname: O'Loughlin
authors.forename: Zinan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Albert
authors.initials: A
authors.lastname: Siryaporn
authors.forename: Justin E
authors.initials: JE
authors.lastname: Silpe
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
authors.forename: Martin F
authors.initials: MF
authors.lastname: Semmelhack
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D011710:Pyocyanine / Q000096:biosynthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D011725:Pyridines; D054852:Small Molecule Libraries; D011710:Pyocyanine