Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase-Catalyzed Systems

Abstract

Antibiotic resistance is an increasingly serious threat to global health. Consequently, the development of non-antibiotic based therapies and disinfectants, which avoid induction of resistance, or cross-resistance, is of high priority. We report the synthesis of a biocidal complex, which is produced by the reaction between ionic oxidizable salts—iodide and thiocyanate—in the presence of hydrogen peroxide as an oxidation source. The reaction generates bactericidal reactive oxygen and iodine species. In this study, we report that the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with activity against planktonic and biofilm cells of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and methicillin-resistant S. aureus) bacteria. The minimum bactericidal concentrations and the minimum biofilm eradication concentrations of the biocidal composite were in the range of 7.8–31.3 and 31.3–250 μg ml−1, respectively. As a result, the complex was capable to cause a rapid cell death of planktonic test cultures at between 0.5 and 2 h, and complete eradication of dual and mono-species biofilms between 30 s and 10 min. Furthermore, the test bacteria, including a MRSA strain, exposed to the cocktail failed to develop resistance after serial passages. The antimicrobial activity of the ITC appears to derive from the combinational effect of the powerful species capable of oxidizing the essential biomolecules of bacteria. The use of this composition may provide an effective and efficient method for killing potential pathogens, as well as for disinfecting and removing biofilm contamination.

Comparison of thiocyanate and selenocyanate for potentiation of antimicrobial photodynamic therapy

“…An antimicrobial mouth rinse was devised to take advantage of naturally occurring salivary peroxidases, which contained 4 mM H 2 O 2 and 1 mM KSCN at pH 5.5 . Tonoyan et al described an antibacterial system containing H 2 O 2 , thiocyanate and iodide that produced antibacterial ROS and iodine species under the action of peroxidases . Can selenocyanate improve upon these antimicrobial applications of thiocyanate?…”

In vitro comparative cytotoxicity study of a novel biocidal iodo-thiocyanate complex

“…Eight two-fold dilutions of the selected antimicrobials were tested, and the concentrations in the wells ranged from 7.8 to 1000 µg ml -1 . As it was shown previously (Tonoyan et al 2017), that ITC at this specified concentration range could eradicate E. coli biofilms within 10 min, this was thus considered an appropriate duration of exposure to demonstrate antimicrobial activity. Following the 10 min incubations, 10 µl aliquots were taken from the supernatant and ten-fold serially diluted in PBS.…”

“…All the materials were purchased from Sigma-Aldrich, unless otherwise stated. The antimicrobial agents evaluated in this study were H2O2/KI, H2O2/KSCN and H2O2/KI/KSCN [ITC; (Tonoyan et al 2017)]. The stock solutions were prepared by combining concentrated solutions of H2O2 (v/v) with KI (w/v) and/or KSCN (w/v) to obtain 1% final concentrations for each agent.…”

“…Peroxidase-catalyzed systems may also inspire the development of a new generation of antimicrobial agents. Our previous research evaluated three such antimicrobial agents (Tonoyan et al 2017). The agents, all produced without a peroxidase enzyme, were formed by the reactions of H2O2 with iodide (I -) salt (H2O2/KI); or H2O2 with thiocyanate (SCN -) salt (H2O2/KSCN); or H2O2 with both ion substrates (Iand SCN -).…”

“…Genotoxicity testing is also an important aspect of the safety assessment of broad-spectrum substances, including pharmaceuticals and biocides (Corvi and Madia 2016). Our previous research (Tonoyan et al 2017) indicated that the ITC contains reactive species, which may have the potential to induce bacterial DNA breakage; the detection of DNA breaks by single cell gel electrophoresis (comet assay), would thus be informative.…”