title: N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: In vitro anti-virulence activity and metabolic stability.
abstract: ExsA is a multiple adaptational response (MAR) transcription factor, regulating the expression of a virulence determinant, the type III secretion system (T3SS) in Pseudomonas aeruginosa. Non-cytotoxic, non-antibacterial N-hydroxybenzimidazoles were identified as effective inhibitors of ExsA-DNA binding, and their potential utility as anti-virulence agents for P. aeruginosa was demonstrated in a whole cell assay. Select N-hydroxybenzimidazole inhibitors were stable in an in vitro human liver microsomal assay.
authors.affiliation: Paratek Pharmaceuticals, Inc. 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Grier
authors.forename: Lynne K
authors.initials: LK
authors.lastname: Garrity-Ryan
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Bartlett
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Klausner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Donovan
authors.forename: Caroline
authors.initials: C
authors.lastname: Dudley
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alekshun
authors.forename: S Ken
authors.initials: SK
authors.lastname: Tanaka
authors.forename: Michael P
authors.initials: MP
authors.lastname: Draper
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Levy
authors.forename: Oak K
authors.initials: OK
authors.lastname: Kim
mesh_terms: D001562:Benzimidazoles / Q000037:antagonists & inhibitors*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014774:Virulence / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D014157:Transcription Factors