Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly - Institut Pasteur Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2019

Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly

Abstract

Despite the availability of antibiotics and vaccines, Neisseria meningitidis 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.
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Dates and versions

pasteur-03100484 , version 1 (18-01-2021)

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Flore Aubey, Jean-Philippe Corre, Youxin Kong, Ximing Xu, Dorian Obino, et al.. Inhibitors of the Neisseria meningitidis PilF ATPase provoke type IV pilus disassembly. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (17), pp.8481-8486. ⟨10.1073/pnas.1817757116⟩. ⟨pasteur-03100484⟩
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