Format

Send to

Choose Destination
Int J Antimicrob Agents. 2019 Jul;54(1):85-88. doi: 10.1016/j.ijantimicag.2019.04.002. Epub 2019 Apr 25.

Disulfiram, an alcohol dependence therapy, can inhibit the in vitro growth of Francisella tularensis.

Author information

1
CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK.
2
CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK. Electronic address: hcfsmith@dstl.gov.uk.
3
Instituto Gulbenkian de Ciência, Oeiras, Portugal; Ophiomics - Precision Medicine, Lisbon, Portugal.
4
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
5
Thelial Technologies S.A., Lisbon, Portugal.
6
CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK; Biosciences, University of Exeter, Exeter, UK.

Abstract

Disulfiram (DSF) can help treat alcohol dependency by inhibiting aldehyde dehydrogenase (ALDH). Genomic analysis revealed that Francisella tularensis, the causative agent of tularemia, has lost all but one ALDH-like domain and that this domain retains the target of DSF. In this study, minimum inhibitory concentration (MIC) assays demonstrated that both DSF and its primary metabolite diethyldithiocarbamate (DDC) have strong antimicrobial activity against F. tularensis strain SCHU S4, with the MIC of DSF determined as 2 µg/mL in comparison with 8 µg/mL for DDC. The activity of DSF was further confirmed using an in vitro human macrophage infection assay. Francisella tularensis bacteria in DSF-treated cells were reduced in comparison with untreated and DDC-treated cells, comparable with that observed in doxycycline-treated cells. This suggests that DSF may be suitable for further investigation as an in vivo therapy for tularemia.

KEYWORDS:

Bioinformatics; Disulfiram; Drug repurposing; Francisella tularensis; MIC

Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center