diamide and malic-acid

Dozens of Gram negative pathogens use one or more type III secretion systems (T3SS) to disarm host defenses or occupy a beneficial niche during infection of a host organism. While the T3SS represents an attractive drug target and dozens of compounds with T3SS inhibitory activity have been identified, few T3SS inhibitors have been validated and mode of action determined. One issue is the lack of standardized orthogonal assays following high throughput screening. Using a training set of commercially available compounds previously shown to possess T3SS inhibitory activity, we demonstrate the utility of an experiment pipeline comprised of six distinct assays to assess the stages of type III secretion impacted: T3SS gene copy number, T3SS gene expression, T3SS basal body and needle assembly, secretion of cargo through the T3SS, and translocation of T3SS effector proteins into host cells. We used enteropathogenic

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Secretion Systems; Diamide; Gene Dosage; Gene Expression Regulation, Bacterial; Genes, Bacterial; Malates; Plasmids; Protein Tyrosine Phosphatases; Type III Secretion Systems; Virulence; Yersinia; Yersinia pseudotuberculosis