Characterizing a novel antimicrobial molecule effective for drug-resistant pathogens and bacterial biofilm that augments keratinocyte migration

Abstract

Hypervalent silver complexes, containing Ag(II) and Ag(III), have recently gained interest due to their potent antimicrobial efficacy. This work explores the synthesis and antimicrobial activity of a novel tribasic silver bisperiodate tetrahydrate (K3AgBP) complex containing both silver and iodine in hypervalent states: Ag(III) and I(VII). The antimicrobial efficacy of K3AgBP was evaluated and compared to hypervalent silver oxynitrate (Ag7NO11) and periodate salts, and conventional antibiotic drug compounds against methicillin-susceptible (MSSA) and resistant Staphylococcus aureus (USA-300 MRSA), susceptible (PAO1) and carbapenem-resistant blaVIM-2-positive (VIM-2) Pseudomonas aeruginosa, and drug-resistant strains of Candida. Minimum inhibitory concentrations for K3AgBP were equal or lower than silver oxynitrate and periodate salts for all species tested and significantly lower than antibiotics against MRSA, VIM-2 and antifungal efficacy against clinically isolated resistant C. albicans (Ca3917) was also shown. Hypervalent silvers, impregnated in a dressing at 0.4 mg Ag/cm2, were evaluated against 72-hour established biofilm. K3AgBP more effectively (P < 0.05) disrupted and eradicated S. aureus and P. aeruginosa biofilm, 6.72 ± 0.23 and 6.81 ± 0.23 log reduction within 4-hours and 2-hours respectively, versus 4.33 ± 0.23 and 4.97 ± 0.68 log CFU/ml respectively for silver oxynitrate. To assess possible cytotoxicity, viability of cultured HaCat keratinocytes treated with K3AgBP or hypervalent silver oxynitrate was determined using an MTT assay. Treatment with 1 or 10 µM K3AgBP or Ag7NO11 for 2 or 24 h did not cause a significant reduction in cell viability. Signficanty, 10 µM K3AgBP augmented HaCat cell migration. Absence of cytotoxicity along with the unexpected effects on migration, as well as stability and antimicrobial and antibiofilm efficacy support the potential application of K3AgBP as a topical antimicrobial.