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Article Dans Une Revue iScience Année : 2022

C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus

Amel Mettouchi
Emmanuel Lemichez

Résumé

The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways. C910 protects cells against eight bacterial AB toxins and the CNF1-mediated pathogenic Escherichia coli invasion. Interestingly, C910 reduces influenza A H1N1 and SARS-CoV-2 viral infection in vitro. Moreover, parenteral administration of C910 to mice resulted in its accumulation in lung tissues and a reduction in lethal influenza infection.
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Dates et versions

inserm-03741921 , version 1 (02-08-2022)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Yu Wu, Nassim Mahtal, Eléa Paillares, Léa Swistak, Sara Sagadiev, et al.. C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus. iScience, 2022, 25 (7), pp.104537. ⟨10.1016/j.isci.2022.104537⟩. ⟨inserm-03741921⟩
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