1. Disulfiram, an alcohol dependence therapy, can inhibit the in vitro growth of Francisella tularensis
- Author
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Helen S. Atkins, Helen C. Flick-Smith, José B. Pereira-Leal, Richard Hampson, Kay B. Barnes, Jaroslaw Surkont, Karleigh A. Hamblin, and Sarah V. Harding
- Subjects
0301 basic medicine ,Microbiology (medical) ,THP-1 Cells ,030106 microbiology ,Acetaldehyde Dehydrogenase Inhibitors ,Aldehyde dehydrogenase ,Microbial Sensitivity Tests ,Monocytes ,Microbiology ,Tularemia ,03 medical and health sciences ,Minimum inhibitory concentration ,0302 clinical medicine ,In vivo ,Disulfiram ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Francisella tularensis ,biology ,Chemistry ,General Medicine ,biology.organism_classification ,Antimicrobial ,medicine.disease ,Bacterial Load ,In vitro ,Anti-Bacterial Agents ,Infectious Diseases ,biology.protein ,Alcohol Deterrents ,medicine.drug - 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.
- Published
- 2019