Whole Cell Luminescence-Based Screen for Inhibitors of the Bacterial Sec Machinery.

ABSTRACT: There is a pressing need for new antibiotics to combat rising resistance to those already in use. The bacterial general secretion (Sec) system has long been considered a good target for novel antimicrobials thanks to its irreplacable role in maintaining cell envelope integrity, yet the lack of a robust, high-throughput method to screen for Sec inhibition has so far hampered efforts to realize this potential. Here, we have adapted our recently developed in vitro assay for Sec activity─based on the split NanoLuc luciferase─to work at scale and in living cells. A simple counterscreen allows compounds that specifically target Sec to be distinguished from those with other effects on cellular function. As proof of principle, we have applied this assay to a library of 5000 compounds and id

SUBMITTER: Salter T 

PROVIDER: S-EPMC11411707 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature