Characterization of a novel antimicrobial agent inspired by peroxidase-catalyzed systems

The phenomenon of antibiotic resistance is expanding and the threat regarding our future ability to combat infection is increasing. Thus, key challenges for society and for researchers are to address microbial drug resistance and to develop non-antibiotic based therapies and disinfectants that can avoid induction of resistance. A novel antibacterial complex was developed, drawing the inspiration from naturally occurring peroxidase-catalyzed systems that play a role in immune defense against invading microbes. In the peroxidase system, a particular peroxidase enzyme catalyzes the oxidation of a halide/pseudohalide, at the expense of hydrogen peroxide (H2O2), to generate reactive products with broad antimicrobial properties. However, producing enzymes in quantities widely usable for antibacterial treatments would be both expensive and impractical. In the new peroxidase-like antibacterial complex, it is H2O2 that oxidizes the two halide/pseudohalide substrates (iodide and thiocyanate) in the absence of a peroxidase. This enzyme-free iodo-thiocyanate complex (ITC) is a mixture of highly reactive oxygen and iodine species that can damage bacterial cells, resulting in their death. The objective of this thesis was, firstly, to evaluate the antibacterial properties of ITC. The antibacterial potential of the novel ITC was tested on two Gram-negative and two Gram-positive bacterial strains, including the multidrug-resistant Staphylococcus aureus, in both planktonic and biofilm forms. The results of this study showed that the iodo-thiocyanate complex caused rapid bacterial death in all tested strains, both in biofilms and planktonic cells. Furthermore, the attempts to introduce resistance in these bacteria towards the “killer cocktail”, employing a sequential passage of bacteria in the presence of a sub-lethal concentration of ITC, proved to be not successful. Though the knowledge on the mode of action of the antimicrobial complex is still incomplete, there are indications that its antimicrobial activity is most likely the ...