Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa.

TitleDevelopment of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa.
Publication TypeJournal Article
Year of Publication2015
AuthorsMiller, LC, O'Loughlin, CT, Zhang, Z, Siryaporn, A, Silpe, JE, Bassler, BL, Semmelhack, MF
JournalJ Med Chem
Volume58
Issue3
Pagination1298-306
Date Published2015 Feb 12
ISSN1520-4804
KeywordsAmides, Anti-Bacterial Agents, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Molecular Structure, Pseudomonas aeruginosa, Pyocyanine, Pyridines, Small Molecule Libraries, Structure-Activity Relationship
Abstract

<p>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.</p>

DOI10.1021/jm5015082
Alternate JournalJ. Med. Chem.
PubMed ID25597392
PubMed Central IDPMC4332565
Grant List5R01GM065859 / GM / NIGMS NIH HHS / United States
F32 AI095002 / AI / NIAID NIH HHS / United States
F32AI095002 / AI / NIAID NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States