Title | Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Miller, LC, O'Loughlin, CT, Zhang, Z, Siryaporn, A, Silpe, JE, Bassler, BL, Semmelhack, MF |
Journal | J Med Chem |
Volume | 58 |
Issue | 3 |
Pagination | 1298-306 |
Date Published | 2015 Feb 12 |
ISSN | 1520-4804 |
Keywords | Amides, 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> |
DOI | 10.1021/jm5015082 |
Alternate Journal | J Med Chem |
PubMed ID | 25597392 |
PubMed Central ID | PMC4332565 |
Grant List | F32 AI095002 / AI / NIAID NIH HHS / United States R01 GM065859 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States / / Howard Hughes Medical Institute / United States F32AI095002 / AI / NIAID NIH HHS / United States 5R01GM065859 / GM / NIGMS NIH HHS / United States |