Albumin enhances caspofungin activity against Aspergillus species by facilitating drug delivery to germinating hyphae.
Antimicrob Agents Chemother. 2015 Dec 7;
Authors: Ioannou P, Andrianaki A, Akoumianaki T, Kyrmizi I, Albert N, Perlin D, Samonis G, Kontoyiannis DP, Chamilos G
The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥ 4-fold decrease in MECs values (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp in cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescent-labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture media with albumin resulted in a significant 5-fold, increase in association of fluorescent-labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae.
PMID: 26643329 [PubMed - as supplied by publisher]