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 lg/ml inhibited the growth of Staphylococcus aureus by 71.2 % and Candida albicans by 86.2 % in vitro. Larvae inoculated with 20 ll of SBC3 solution showed no ill effects up to a concentration of 250 lg/ml but administration of 500 lg/ml resulted in a 40 % reduction in larval survival and administration of a dose of 1,000 lg/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 ll SBC3 solution of 100 lg/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.

Silver coordination compounds: A new horizon in medicine

“…albicans [50]. After the complex, at a concentration of 25 μg/ml, inhibited the growth of S. aureus by 71.2% and C. albicans by 86.2% in vitro, administration of SBC3 to inoculated larvae resulted in increased survival.…”

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

“…The benefit of this is that the inoculum and the treatment are controlled. G. mellonella is useful for in vivo treatment with conventional antifungal drugs (Coleman et al, 2011; de Lacorte Singulani et al, 2016), for assessing antifungal synergistic activity (Gu et al, 2016; Sangalli-Leite et al, 2016) and for evaluating the in vivo efficacy of new drug candidates (Browne et al, 2014). …”

Raf-Kinase Inhibitor Gw5074 Shows Antibacterial Activity Against Methicillin-Resistant Staphylococcus Aureus and Potentiates the Activity of Gentamicin

“…These similarities facilitated the study of staphylococcal pathogenesis using this model as a host [42][43][44]. The G. mellonella infection model is also a quick and inexpensive way to test the efficacy of antimicrobial agents against S. aureus in vivo [29,45,46]. Altogether, the combination of these two models allowed us to first identify the antimicrobial agents and then evaluate their antimicrobial activity against S. aureus without exposing mammalian hosts.…”