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Identifier

000382523

Title

Dissecting the echinocandin paradoxical activity against aspergillus fumigatus

Alternative Title

Διερεύνηση του παράδοξου των εχινοκάνδινων εναντίον του μύκητα aspergillus fumigatus

Author

Ιωάννου, Πέτρος

Thesis advisor

Χαμηλός, Γιώργος

Reviewer

Σιδηρόπουλος, Πρόδρομος
Μπερτσιάς, Γιώργος

Abstract

Echinocandins comprise a novel class of antifungal compounds with potent in vivo activity against Candida and Aspergillus. However, despite causing morphologic changes in germinating hyphae of Aspergillus, echinocandins fail to inhibit fungal growth in vitro. This paradoxical lag in in vitro activity of echinocandins against Aspergillus implies the presence of additional mechanisms of action of these antifungal agents in vivo. Echinocandin-mediated β-1,3 glucan exposure in Aspergillus hyphae triggers activation of potent immune responses and could represent an alternative mechanism of action of these compounds. However, the precise mechanisms of echinocandin induced augmention of in vivo activity have not been characterized. In this study, we attempted to decode this echinocandin paradox. By performing in vitro experiments in conditions of high (5%) CO2, we attempted to simulate in vivo growth of Aspergillus fumigatus in tissue, and noticed a significant increase in echinocandin activity. Additionally, we found that Aspergillus fumigatus hyphae pre-treated with caspofungin showed a remarkably enhanced exposure of β-1,3 glucan. Surprisingly, caspofungin treated hyphae presented significantly more damage after osmotic shock compared to the untreated controls. Of interest, we did not find a significant enhancement in neutrophil activity against Aspergillus upon pretreatment with echinocandins. Collectively, these data could partially explain the echinocandin paradoxical activity against Aspergillus, and provide a simple method for a more accurate and reliable estimation of in vitro activity of these compounds against Aspergillus fumigatus.

Language

English

Subject

Aspergillus

Caspofungin

Echinocandins

Fumigatus

Ασπεργίλλος

Εχινοκάνδινες

Κασποφουγκίνη

Issue date

2013-07-16