Location: Foodborne Toxin Detection and Prevention Research
Title: Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virusAuthor
LEONARDI, WILLIAM - Keck Graduate Institute | |
ZILBERMINTZ, LEEOR - Keck Graduate Institute | |
Cheng, Luisa | |
ZOZAYA, JOSUE - Keck Graduate Institute | |
TRAN, SHARON - Keck Graduate Institute | |
ELLIOTT, JEFFREY - Keck Graduate Institute | |
POLUKHINA, KSENIYA - Keck Graduate Institute | |
MANASHEROB, ROBERT - Stanford University | |
LI, AMY - Stanford University | |
CHI, XIAOLI - Us Army Medical Research Institute | |
GHARAIBEH, DIMA - Us Army Medical Research Institute | |
KENNY, TARA - Us Army Medical Research Institute | |
ZAMANI, ROUZBEH - Us Army Medical Research Institute | |
SOLOVEVA, VERONICA - Us Army Medical Research Institute | |
HADDOW, ANDREW - Us Army Medical Research Institute | |
NASAR, FAROOQ - Us Army Medical Research Institute | |
BAVARI, SINA - Us Army Medical Research Institute | |
BASSIK, MICHAEL - Stanford University | |
COHEN, STANLEY - Stanford University | |
LEVITIN, ANASTASIA - Keck Graduate Institute | |
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. |