Why is disulfiram generally ineffective against most Gram-negative organisms, and which Gram-negative bacteria does it affect?

Label:chem

Topic
Disulfiram's activity against Gram-negative bacteria is limited.
Answer
Disulfiram does not inhibit the growth of most Gram-negative organisms, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, or Vibrio cholerae (MIC > 32 µg/mL). This is believed to be due to the antagonistic effects of glutathione, abundant in Gram-negative organisms, which reacts readily with disulfiram, cleaving it into diethyldithiocarbamate (DDTC). Unlike disulfiram, DDTC lacks the disulfide bond necessary for thiol-disulfide exchange to inhibit essential bacterial enzymes, resulting in no antibacterial activity against most Gram-positive organisms either. However, disulfiram has been shown to kill some Gram-negative organisms in vitro, including Borrelia burgdorferi (0.19–1.48 µg/mL), Francisella tularensis (0.50–9.50 µg/mL), and Bartonella henselae (2.5 µg/mL), and also shows activity against the atypical bacteria Mycoplasma spp. (0.19 µg/mL).
Return to Home Chemical List
Knowledge you may be interested in
How effective is disulfiram against Gram-positive bacteria, and particularly against resistant strains? What is the mechanism by which disulfiram is thought to treat cocaine addiction? How does disulfiram help in the treatment of alcohol use disorder? What are the possible metabolic fates of diethyldithiocarbamate (DDTC)? What are the absorption and distribution characteristics of disulfiram? How does disulfiram influence the concentration of reactive oxygen species (ROS) within cells? What is the role of the disulfide bond in disulfiram's mechanism of action? How does disulfiram's metabolite, diethyldithiocarbamate (DDTC), affect metal-containing enzymes? How does Disulfiram work to prevent alcohol use disorder (AUD) reoccurrence? Why is fluoroethylene carbonate (FEC) essential for initiating methyl methacrylate (MMA) polymerization with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)? What is disulfiram primarily used for and what new treatment potential has been identified? How does disulfiram affect leukemia cells? How does disulfiram's cytotoxic activity compare between leukemia cells and other cell types? Why might disulfiram cause parkinsonism? Why is 2-Ethylhexyl acrylate (2-EHA) used in the polymer industry? What compounds were used as soft monomers in the preparation of the aqueous emulsion acrylic adhesive? What compounds were used as hard monomers? And what compounds were used as hydrophilic functional monomers? Why is Ergothioneine considered a valuable compound? What are the primary antioxidant mechanisms of Ergothioneine (ERG)? Why does Ergothioneine primarily exist in its thione form under physiological conditions? How does Ergothioneine's stability compare to other thiols and antioxidants in organisms?