title: Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae.
abstract: The antimicrobial drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate (SBC3) was evaluated for its ability to function in vivo using larvae of Galleria mellonella. A SBC3 concentration of 25 μg/ml inhibited the growth of Staphylococcus aureus by 71.2% and Candida albicans by 86.2% in vitro. Larvae inoculated with 20 μl of SBC3 solution showed no ill effects up to a concentration of 250 μg/ml but administration of 500 μg/ml resulted in a 40% reduction in larval survival and administration of a dose of 1,000 μg/ml resulted in total larval death at 24 h. Larvae inoculated with S. aureus or C. albicans and subsequently administered SBC3 showed increased survival. Administration of SBC3 to larvae did not boost the insect immune response as indicated by lack of an increase in the density of circulating haemocytes (immune cells). The abundance of a number of proteins involved in the insect immune response was reduced in larvae that received 20 μl SBC3 solution of 100 μg/ml. This is the first demonstration of the in vivo activity of SBC3 against S. aureus and C. albicans and demonstrates that SBC3 does not stimulate a non-specific immune response in larvae.
authors.affiliation: Department of Biology, National University of Ireland Maynooth, Co Kildare, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Browne
authors.forename: Frauke
authors.initials: F
authors.lastname: Hackenberg
authors.forename: Wojciech
authors.initials: W
authors.lastname: Streciwilk
authors.forename: Matthias
authors.initials: M
authors.lastname: Tacke
authors.forename: Kevin
authors.initials: K
authors.lastname: Kavanagh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology; D048288:Imidazolines / Q000494:pharmacology*; D056724:Immunity, Humoral; D019476:Insect Proteins / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009942:Organometallic Compounds / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology
chemical_list: C000596364:1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D048288:Imidazolines; D019476:Insect Proteins; D009942:Organometallic Compounds