Impact of Target Turnover on the Translation of Drug-Target Residence Time to Time-Dependent Antibacterial Activity.

ABSTRACT: The translation of time-dependent drug-target occupancy to extended pharmacological activity at low drug concentration depends on factors such as target vulnerability and the rate of target turnover. Previously, we demonstrated that the postantibiotic effect (PAE) caused by inhibitors of bacterial drug targets could be used to assess target vulnerability, and that high levels of target vulnerability coupled with relatively low rates of target resynthesis resulted in a strong correlation between drug-target residence time and the PAE following compound washout. Although the residence time of inhibitors on UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) in Pseudomonas aeruginosa (paLpxC) results in significant PAE, inhibitors of the equivalent enzyme in Escherichi

SUBMITTER: Basu R 

PROVIDER: S-EPMC8791448 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature