Cobalt bis-dicarbollide and its ammonium derivatives are effective antimicrobial and antibiofilm agents

The failure of currently used antibiotics in infections treatment caused by still often emerging microbial resistance is one of the most important worldwide research items. Based on the proved biological activities of cobalt bis-dicarbollide anion [1]- and its derivatives in many medical fields, we tested the sodium salt of cobalt bis-dicarbollide Na[1], and its two ammonium derivatives 8-NH3-[1], 8- PhNH2-[1] to confirm their antimicrobial and, to the best of our knowledge, to demonstrate as first their antibiofilm action. The representatives of the opportunistic pathogens of gram-positive (Staphylococcus spp. and Enterococcus faecalis) and gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), yeast Candida parapsilosis and filamentous fungus Trichosporon cutaneum were chosen. Antimicrobial activity was determined by minimum inhibitory concentrations (MIC80) and antibiofilm activity determination was based on MTT assay, crystal violet staining and visualization by microscopic methods. Cytotoxicity against human embryonic kidney cells HEK 293T was measured using resazurin assay. Antimicrobial activity of Na[1], 8-NH3-[1], 8-PhNH2-[1] was significant for gram-positive bacteria and T. cutaneum at non-cytotoxic concentrations of about 5 mu g/mL while other microorganisms were not sensitive up to 90 mu g/mL. Significant antibiofilm effect was observed with Na[1] in gram-positive bacteria whose biofilm formation was inhibited by at least 80% at 50 mu g/mL. In contrast to the selective antibiofilm activity of 8-PhNH2-[1] which prevents T. cutaneum biofilm formation at 1 mu g/mL, other microorganisms were almost unaffected. Our results provided the first evidence about antibiofilm activity of cobalt bis-dicarbollide against gram-positive bacteria as well as the possibility of extending its usage to include the treatment of infections caused by other types of microorganisms by preparing and using its derivatives. (C) 2019 Elsevier B.V. All rights reserved.