title: Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae.
abstract: 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 minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently 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 medium with albumin resulted in a significant, 5-fold increase in association of fluorescently 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.
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Ioannou
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Andrianaki
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Tonia
authors.initials: T
authors.lastname: Akoumianaki
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Kyrmizi
authors.affiliation: Department of Infectious Diseases, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Albert
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Perlin
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Samonis
authors.affiliation: Department of Infectious Diseases, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA dkontoyi@mdanderson.org hamilos@imbb.forth.gr.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Department of Medicine, University of Crete, Heraklion, Crete, Greece dkontoyi@mdanderson.org hamilos@imbb.forth.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
mesh_terms: D000418:Albumins / Q000378:metabolism / Q000494:pharmacology*; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D000077336:Caspofungin; D003470:Culture Media / Q000737:chemistry; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000418:Albumins; D000935:Antifungal Agents; D003470:Culture Media; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D065819:Voriconazole; D000077551:Micafungin