Skip to main content
ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #328484

Research Project: Advance the Development of Technologies for Detecting and Determining the Stability and Bioavailability of Toxins that Impact Food Safety and Food Defense

Location: Foodborne Toxin Detection and Prevention Research

Title: Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

Author
item LEONARDI, WILLIAM - Keck Graduate Institute
item ZILBERMINTZ, LEEOR - Keck Graduate Institute
item Cheng, Luisa Wai Wai
item ZOZAYA, JOSUE - Keck Graduate Institute
item TRAN, SHARON - Keck Graduate Institute
item ELLIOTT, JEFFREY - Keck Graduate Institute
item POLUKHINA, KSENIYA - Keck Graduate Institute
item MANASHEROB, ROBERT - Stanford University
item LI, AMY - Stanford University
item CHI, XIAOLI - Us Army Medical Research Institute
item GHARAIBEH, DIMA - Us Army Medical Research Institute
item KENNY, TARA - Us Army Medical Research Institute
item ZAMANI, ROUZBEH - Us Army Medical Research Institute
item SOLOVEVA, VERONICA - Us Army Medical Research Institute
item HADDOW, ANDREW - Us Army Medical Research Institute
item NASAR, FAROOQ - Us Army Medical Research Institute
item BAVARI, SINA - Us Army Medical Research Institute
item BASSIK, MICHAEL - Stanford University
item COHEN, STANLEY - Stanford University
item LEVITIN, ANASTASIA - Keck Graduate Institute
item MARTCHENKO, MIKHAIL - Keck Graduate Institute

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2016
Publication Date: 9/30/2016
Publication URL: http://handle.nal.usda.gov/10113/5678135
Citation: Leonardi, W., Zilbermintz, L., Cheng, L.W., Zozaya, J., Tran, S.H., Elliott, J.H., Polukhina, K., Manasherob, R., Li, A., Chi, X., Gharaibeh, D., Kenny, T., Zamani, R., Soloveva, V., Haddow, A., Nasar, F., Bavari, S., Bassik, M., Cohen, S.N., Levitin, A., Martchenko, M. 2016. Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus. Scientific Reports. 6:34475. doi: 10.1038/srep34475.

Interpretive Summary: The human body responds to assault by different toxins and pathogens with various host defense pathways. In this study, scientists devised a screening method to identify drugs that prevent toxicity from different bacterial or viral pathogens by targeting the caspase response pathways. The drug bithionol was identified as an inhibitor of caspases and was shown to inhibit or reduce the toxicity of diphtheria, cholera, Pseudomonas aeruginosa exotoxin A, and botulinum neurotoxin serotype A toxins as well as the Zika virus. Targeting host defense pathways would represent a new therapeutic approach to prevent infectious diseases.

Technical Abstract: Disease pathways form overlapping networks, and hub proteins represent attractive targets for broad-spectrum drugs. Using bacterial toxins as a proof of concept, we describe a new approach of discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it intertwines cellular-based with protein function-based multiplex drug screens and thus concurrently discovers therapeutic compounds and their protein targets. We discovered that a previously approved drug, Bithionol, reduces detrimental effects of multiple deadly toxins and of Zika virus by inhibiting host hub proteins such as caspases. Moreover, the anti-toxin potential of Bithionol was demonstrated in B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European, and Asian ancestry.