N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: In vitro anti-virulence activity and metabolic stability.
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.
Grier
Mark C
MC
Paratek Pharmaceuticals, Inc. 75 Kneeland Street, Boston, MA 02111, USA.
Garrity-Ryan
Lynne K
LK
Bartlett
Victoria J
VJ
Klausner
Kevin A
KA
Donovan
Peter J
PJ
Dudley
Caroline
C
Alekshun
Michael N
MN
Tanaka
S Ken
SK
Draper
Michael P
MP
Levy
Stuart B
SB
Kim
Oak K
OK
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*
D001562:Benzimidazoles; D014157:Transcription Factors