MurF Inhibitors with Antibacterial Activity: Effect on Muropeptide Levels ▿: Influence Statistics

Expert Impact

Concepts for which they have has direct influence: Murf inhibitors , Antibacterial activity , Cytoplasmic step , Bacterial survival , Bacterial cell , Staphylococcus aureus , Enterococcus faecium .

Key People For Murf Inhibitors

Top KOLs in the world
#1
Roger C Levesque
pseudomonas aeruginosa salmonella enterica spruce budworm
#2
François Sanschagrin
pseudomonas aeruginosa breast cancer inflammatory markers
#3
Ahmed El Zoeiby
pseudomonas aeruginosa outer membranes mur enzymes
#4
Timothy D H Bugg
escherichia coli rhodococcus jostii lignin oxidation
#5
Philip J Hajduk
drug design protein tyrosine nuclear magnetic resonance
#6
Claude G Lerner
escherichia coli alarm nmr antibacterial agents
Similar searches    murf inhibitors , murf inhibitors dq1

MurF Inhibitors with Antibacterial Activity: Effect on Muropeptide Levels ▿

Abstract

. MurF catalyzes the last cytoplasmic step of bacterial cell wall synthesis and is essential for bacterial survival. Our previous studies used a pharmacophore model of a MurF inhibitor to identify additional inhibitors with improved properties. We now present the characterization of two such inhibitors, the diarylquinolines DQ1 and DQ2. DQ1 inhibited Escherichia coli MurF (50% inhibitory concentration, 24 microM) and had modest activity (MICs, 8 to 16 microg/ml) against lipopolysaccharide (LPS)-defective E. coli and wild-type E. coli rendered permeable with polymyxin B nonapeptide. DQ2 additionally displayed activity against gram-positive bacteria (MICs, 8 to 16 microg/ml), including methicillin (meticillin)-susceptible and -resistant Staphylococcus aureus isolates and vancomycin-susceptible and -resistant Enterococcus faecalis and Enterococcus faecium isolates. Treatment of LPS-defective E. coli cells with >or=2x MIC of DQ1 resulted in a 75-fold-greater accumulation of the MurF substrate compared to the control, a 70% decline in the amount of the MurF product, and eventual cell lysis, consistent with the inhibition of MurF within bacteria. DQ2 treatment of S. aureus resulted in similar effects on the MurF substrate and product quantities. At lower levels of DQ1 (