Novel compounds targeting the enterohemorrhagic Escherichia coli type three secretion system reveal insights into mechanisms of secretion inhibition.

ABSTRACT: Anti-virulence (AV) compounds are a promising alternative to traditional antibiotics for fighting bacterial infections. The Type Three Secretion System (T3SS) is a well-studied and attractive AV target, given that it is widespread in more than 25 species of Gram-negative bacteria, including enterohemorrhagic E. coli (EHEC), and as it is essential for host colonization by many pathogens. In this work, we designed, synthesized and tested a new series of compounds that block the functionality of the T3SS of EHEC. Affinity chromatography experiments identified the primary target of the compounds as the T3SS needle pore protein EspD, which is essential for effector protein translocation into host cells. These data were supported by mechanistic studies that determined the coiled-coil domain 1 of

SUBMITTER: Zambelloni R 

PROVIDER: S-EPMC5575525 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature