Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus.

Details

Serval ID
serval:BIB_C34B0A7A63C7
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus.
Journal
Critical Reviews In Microbiology
Author(s)
Lamoth F., Juvvadi P.R., Steinbach W.J.
ISSN
1549-7828 (Electronic)
ISSN-L
1040-841X
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
42
Number
2
Pages
310-321
Language
english
Abstract
Invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. The efficacy of current anti-Aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). The heat shock protein 90 (Hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast Candida albicans. Few studies have addressed its role in filamentous fungi such as Aspergillus fumigatus, in which mechanisms of resistance may differ substantially. Hsp90 is at the center of a complex network involving calcineurin, lysine deacetylases (KDAC) and other client proteins, which orchestrate compensatory repair mechanisms of the cell wall in response to the stress induced by antifungals. In A. fumigatus, Hsp90 is a trigger for resistance to high concentrations of caspofungin, known as the paradoxical effect. Disrupting Hsp90 circuitry by different means (Hsp90 inhibitors, KDAC inhibitors and anti-calcineurin drugs) potentiates the antifungal activity of caspofungin, thus representing a promising novel antifungal approach. This review will discuss the specific features of A. fumigatus Hsp90 and the potential for antifungal strategies of invasive aspergillosis targeting this essential chaperone.
Pubmed
Web of science
Create date
12/04/2016 17:34
Last modification date
20/08/2019 16:38
Usage data