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

Autor: Hamblin KA; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK., Flick-Smith H; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK. Electronic address: hcfsmith@dstl.gov.uk., Barnes KB; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK., Pereira-Leal JB; Instituto Gulbenkian de Ciência, Oeiras, Portugal; Ophiomics - Precision Medicine, Lisbon, Portugal., Surkont J; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Hampson R; Thelial Technologies S.A., Lisbon, Portugal., Atkins HS; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK; Biosciences, University of Exeter, Exeter, UK., Harding SV; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, UK.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2019 Jul; Vol. 54 (1), pp. 85-88. Date of Electronic Publication: 2019 Apr 25.
DOI: 10.1016/j.ijantimicag.2019.04.002
Abstrakt: 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.
(Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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