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Disulfiram, an alcohol dependence therapy, can inhibit the in vitro growth of Francisella tularensis
- Source :
- International Journal of Antimicrobial Agents. 54:85-88
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.
- 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
Subjects
Details
- ISSN :
- 09248579
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- International Journal of Antimicrobial Agents
- Accession number :
- edsair.doi.dedup.....d697af8b1515e3a56917462ddcb61748