Identification of the Hypertension Drug Guanfacine as an Antivirulence Agent in Pseudomonas aeruginosa.

ABSTRACT: An alternative solution to the cyclical development of new antibiotics is the concept of disarming pathogens without affecting their growth, thereby eliminating the selective pressures that lead to resistant phenotypes. Here, we have employed our previously developed HiTES methodology to identify one such compound against the ESKAPE pathogen Pseudomonas aeruginosa. Rather than induce silent biosynthetic gene clusters, we used HiTES to suppress actively expressed virulence genes. By screening a library of 770 FDA-approved drugs, we identified guanfacine, a clinical hypertension drug, as an antivirulence agent in P. aeruginosa. Follow-up studies showed that guanfacine reduces biofilm formation and pyocycanin production without altering growth. Moreover, we identified a homologue of QseC, a s

SUBMITTER: Okada BK 

PROVIDER: S-EPMC6814388 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature