Development of a High Throughput Screen for the Identification of Inhibitors of Peptidoglycan O-Acetyltransferases, New Potential Antibacterial Targets.

ABSTRACT: The O-acetylation of peptidoglycan occurs in many Gram-negative and most Gram-positive pathogens and this modification to the essential wall polymer controls the lytic activity of the autolysins, particularly the lytic transglycosylases, and inhibits that of the lysozymes of innate immunity systems. As such, the peptidoglycan O-acetyltransferases PatA/B and OatA are recognized as virulence factors. In this study, we present the high throughput screening of small compound libraries to identify the first known inhibitors of these enzymes. The fluorometric screening assay developed involved monitoring the respective O-acetyltransferases as esterases using 4-methylumbelliferylacetate as substrate. Pilot screens of 3921 compounds validated the usefulness of the HTS protocol. A number of potenti

SUBMITTER: Brott AS 

PROVIDER: S-EPMC6627197 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature