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Validation of new compounds inhibiting T3SS

Published on 3 October 2020
Targeting the bacterial virulence factors by an anti-virulence strategy represents a promising alternative approach besides antibiotic therapy. Disrupting interactions between components of the T3SS machinery efficiently lowers the bacteria virulence, as shown for the interaction between the needle proteins PscE, PscG and PscF. Using a high-throughput ELISA target-based screening at the CMBA platform (CEA-Grenoble screening facility), we identified several compounds inhibiting the interaction between PscE and PscG. In collaboration with the chemist Yung-Sing Wong (DPM-UGA), the best compounds from each library were selected to build new and larger hybrid analogues that we patented in 2015. Their cellular efficacy and toxicity were recently evaluated using high-content phenotypic analysis. Among these optimized molecules, two leads had a minimal effect on bacterial fitness, were almost nontoxic for eukaryotic cell and specifically inhibited the T3SS and the bacterial virulence ex vivo on cells and in vivo in Galleria mellonella [7].

Ngo TD et al (2019) ACS Infect Dis

[7] Ngo TD et al (2019) ACS Infect Dis. 5(11):1843-1854