Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species.

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Ressource 1Download: serval:BIB_B9C8B817C021.P001 (144.42 [Ko])
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Serval ID
serval:BIB_B9C8B817C021
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species.
Journal
Journal of Antimicrobial Chemotherapy
Author(s)
Lamoth F., Alexander B.D., Juvvadi P.R., Steinbach W.J.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
2015
Volume
70
Number
5
Pages
1408-1411
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
OBJECTIVES: Invasive mould infections are associated with a high mortality rate and the emergence of MDR moulds is of particular concern. Calcineurin and its chaperone, the heat shock protein 90 (Hsp90), represent an important pathway for fungal virulence that can be targeted at different levels. We investigated the antifungal activity of compounds directly or indirectly targeting the Hsp90-calcineurin axis against different mould species.
METHODS: The in vitro antifungal activity of the anticalcineurin drug FK506 (tacrolimus), the Hsp90 inhibitor geldanamycin, the lysine deacetylase inhibitor trichostatin A and the Hsp70 inhibitor pifithrin-μ was assessed by the standard broth dilution method against 62 clinical isolates of Aspergillus spp. and non-Aspergillus moulds (Mucoromycotina, Fusarium spp., Scedosporium spp., Purpureocillium/Paecilomyces spp. and Scopulariopsis spp.)
RESULTS: FK506 had variable antifungal activity against different Aspergillus spp. and was particularly active against Mucor spp. Geldanamycin had moderate antifungal activity against Fusarium spp. and Paecilomyces variotii. Importantly, trichostatin A had good activity against the triazole-resistant Aspergillus ustus and the amphotericin B-resistant Aspergillus terreus as well as the MDR Scedosporium prolificans. Moreover, trichostatin A exhibited synergistic interactions with caspofungin against A. ustus and with geldanamycin against Rhizopus spp. for which none of the other agents showed activity. Pifithrin-μ exhibited little antifungal activity.
CONCLUSIONS: Targeting the Hsp90-calcineurin axis at different levels resulted in distinct patterns of susceptibility among different fungal species. Lysine deacetylase inhibition may represent a promising novel antifungal strategy against emerging resistant moulds.
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2015 14:19
Last modification date
25/09/2019 6:10
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