Auranofin inactivates Trichomonas vaginalis thioredoxin reductase and is effective against trichomonads in vitro and in vivo

Authors

Melissa Hopper, University of the Pacific
Jeong-fil Yun, University of the Pacific
Bianhua Zhou, University of California, San Diego
Christine Le, University of California, San Diego
Katelin Kehoe, University of the Pacific
Ryan Le, University of the Pacific
Ryan I. Hill, University of the PacificFollow
Gregg Jongeward, University of the PacificFollow
Anjan Debnath, University of Montana
Liangfang Zhang, University of California, San Diego
Yukiko Miyamoto, University of California, San Diego
Lars Eckmann, University of California, San Diego
Kirkwood Land, University of the PacificFollow
Lisa Wrischnik, University of the Pacific

ORCID

Dr. Ryan Hill: 0000-0001-8513-6545

Document Type

Article

Publication Title

International Journal of Antimicrobial Agents

Department

Biological Sciences

ISSN

0924-8579

Volume

48

Issue

6

DOI

10.1016/j.ijantimicag.2016.09.020

First Page

690

Last Page

694

Publication Date

December 2016

Abstract

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common, non-viral, sexually transmitted infection in the world, but only two closely related nitro drugs are approved for its treatment. New antimicrobials against trichomoniasis remain an urgent need. Several organic gold compounds were tested for activity against T. vaginalis thioredoxin reductase (TrxR) in cell-free systems as well as for activity against different trichomonads in vitro and in a murine infection model. The organic gold(I) compounds auranofin and chloro(diethylphenylphosphine)gold(I) inhibited TrxR in a concentration-dependent manner in assays with recombinant purified reductase and in cytoplasmic extracts of T. vaginalis transfected with a haemagglutinin epitope-tagged form of the reductase. Auranofin potently suppressed the growth of three independent clinical T. vaginalis isolates as well as several strains of another trichomonad (Tritrichomonas foetus) in a 24 h-assay, with 50% inhibitory concentrations of 0.7–2.5 µM and minimum lethal concentrations of 2–6 µM. The drug also compromised the ability of the parasite to overcome oxidant stress, supporting the notion that auranofin acts, in part, by inactivating TrxR-dependent antioxidant defences. Chloro(diethylphenylphosphine)gold(I) was 10-fold less effective against T. vaginalis in vitro than auranofin. Oral administration of auranofin for 4 days cleared the parasites in a murine model of vaginal T. foetus infection without displaying any apparent adverse effects. The approved human drug auranofin may be a promising agent as an alternative treatment of trichomoniasis in cases when standard nitro drug therapies have failed.

Recommended Citation

Hopper, M., Yun, J., Zhou, B., Le, C., Kehoe, K., Le, R., Hill, R. I., Jongeward, G., Debnath, A., Zhang, L., Miyamoto, Y., Eckmann, L., Land, K., & Wrischnik, L. (2016). Auranofin inactivates Trichomonas vaginalis thioredoxin reductase and is effective against trichomonads in vitro and in vivo. International Journal of Antimicrobial Agents, 48(6), 690–694. DOI: 10.1016/j.ijantimicag.2016.09.020
https://scholarlycommons.pacific.edu/cop-facarticles/508