Identification of the Hypertension Drug Guanfacine as an Antivirulence Agent in Pseudomonas aeruginosa.
Chembiochem
; 20(15): 2005-2011, 2019 08 01.
Article
en En
| MEDLINE
| ID: mdl-30927315
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.â
aeruginosa. Follow-up studies showed that guanfacine reduces biofilm formation and pyocycanin production without altering growth. Moreover, we identified a homologue of QseC, a sensor His kinase used by multiple pathogens to turn on virulence, as a target of guanfacine. Our studies suggest that guanfacine might be an attractive antivirulence lead in P.â
aeruginosa and provide a template for uncovering such molecules by screening for downregulators of actively expressed biosynthetic genes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pseudomonas aeruginosa
/
Guanfacina
/
Factores de Virulencia
/
Antibacterianos
/
Antihipertensivos
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania