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© K. Melican.
Human microvessel (red) colonized by N. meningitidis (green).
Publication : Proceedings of the National Academy of Sciences of the United States of America

Inhibitors of the PilF ATPase provoke type IV pilus disassembly

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 04 Apr 2019

Aubey F, Corre JP, Kong Y, Xu X, Obino D, Goussard S, Lapeyrere C, Souphron J, Couturier C, Renard S, Duménil G

Link to Pubmed [PMID] – 30948644

Proc. Natl. Acad. Sci. U.S.A. 2019 Apr;116(17):8481-8486

Despite the availability of antibiotics and vaccines, remains a major cause of meningitis and sepsis in humans. Due to its extracellular lifestyle, bacterial adhesion to host cells constitutes an attractive therapeutic target. Here, we present a high-throughput microscopy-based approach that allowed the identification of compounds able to decrease type IV pilus-mediated interaction of bacteria with endothelial cells in the absence of bacterial or host cell toxicity. Compounds specifically inhibit the PilF ATPase enzymatic activity that powers type IV pilus extension but remain inefficient on the ATPase that promotes pilus retraction, thus leading to rapid pilus disappearance from the bacterial surface and loss of pili-mediated functions. Structure activity relationship of the most active compound identifies specific moieties required for the activity of this compound and highlights its specificity. This study therefore provides compounds targeting pilus biogenesis, thereby inhibiting bacterial adhesion, and paves the way for a novel therapeutic option for meningococcal infections.

https://www.ncbi.nlm.nih.gov/pubmed/30948644