Repurposing Thiram and Disulfiram as Antibacterial Agents for Multidrug-Resistant Staphylococcus aureus Infections

Abstract

Thiram and disulfiram were evaluated as antibacterial agents against multidrug-resistant Staphylococcus aureus Against a 30-member panel comprised of vancomycin-susceptible, vancomycin-intermediate, and vancomycin-resistant S. aureus strains, the MIC90 values of the respective test agents were 4 and 16 μg/ml. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive-bacterium spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical vancomycin-resistant S. aureus strains in vitro, thus establishing a potential use in combination therapy.

Keywords: MRSA; Staphylococcus aureus; VISA; VRSA; combination therapy; disulfiram; synergy; thiram; vancomycin.

Copyright © 2017 American Society for Microbiology.

Figures

FIG 1

Chemical structures of thiram, disulfiram, and diethyldithiocarbamate.

FIG 2

Effects of thiram (A) and disulfiram (B) on the in vitro growth of S. aureus NCTC 8325.

FIG 3

Effect of thiram, disulfiram, and nisin on cell viability. Shown are the ratios of green to red fluorescence (530/595 nm) for individual groups depicted as means ± the standard errors of the mean (n = 4).