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Open AccessArticle

Revisiting Old Ionophore Lasalocid as a Novel Inhibitor of Multiple Toxins

1
Service d’Ingénierie Moléculaire des Protéines (SIMOPRO), CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France
2
Service de Chimie Bio-organique et Marquage (SCBM), CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France
3
Unité des Toxines Bactériennes, Institut Pasteur, ERL 6002, F-75015 Paris, France
*
Authors to whom correspondence should be addressed.
Toxins 2020, 12(1), 26; https://doi.org/10.3390/toxins12010026
Received: 16 October 2019 / Revised: 9 December 2019 / Accepted: 14 December 2019 / Published: 1 January 2020
(This article belongs to the Special Issue Inhibitors and Countermeasures against Bacterial and Plant Toxins)
The ionophore lasalocid is widely used as a veterinary drug against coccidiosis. We found recently that lasalocid protects cells from two unrelated bacterial toxins, the cytotoxic necrotizing factor-1 (CNF1) from Escherichia. coli and diphtheria toxin. We evaluated lasalocid’s capacity to protect cells against other toxins of medical interest comprising toxin B from Clostridium difficile, Shiga-like toxin 1 from enterohemorrhagic E. coli and exotoxin A from Pseudomonas aeruginosa. We further characterized the impact of lasalocid on the endolysosomal and the retrograde pathways and organelle integrity, especially the Golgi apparatus. We found that lasalocid protects cells from all toxins tested and impairs the drop of vesicular pH along the trafficking pathways that are required for toxin sorting and translocation to the cytoplasm. Lasalocid also has an impact on the cellular distribution of GOLPH4 and GOLPH2 Golgi markers. Other intracellular trafficking compartments positive for EEA1 and Rab9A display a modified cellular pattern. In conclusion, lasalocid protects cells from multiple deadly bacterial toxins by corrupting vesicular trafficking and Golgi stack homeostasis. View Full-Text
Keywords: lasalocid; toxin; Golgi lasalocid; toxin; Golgi
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Mahtal, N.; Wu, Y.; Cintrat, J.-C.; Barbier, J.; Lemichez, E.; Gillet, D. Revisiting Old Ionophore Lasalocid as a Novel Inhibitor of Multiple Toxins. Toxins 2020, 12, 26.

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