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Volume 162, Issue 2

Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of / species complex Free

Abstract

Heat-shock proteins (Hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role in the infectious process. This study investigated the effect of pharmacological inhibition of Hsp90 by radicicol on the / species complex – agents of the most common lifethreatening fungal infection amongst immunocompromised patients. The influence of Hsp90 inhibition was investigated regarding susceptibility to antifungal agents of planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production of virulence factors , and experimental infection in . Hsp90 inhibition inhibited the growth of planktonic cells of spp. at concentrations ranging from 0.5 to 2 μg ml and increased the inhibitory effect of azoles, especially fluconazole (FLC) ( < 0.05). Inhibition of Hsp90 also increased the antifungal activity of azoles against biofilm formation and mature biofilms of spp., notably for . Furthermore, Hsp90 inhibition compromised the permeability of the cell membrane, and reduced planktonic growth at 37 °C and the capsular size of spp. In addition, Hsp90 inhibition enhanced the antifungal activity of FLC during experimental infection using . Therefore, our results indicate that Hsp90 inhibition can be an important strategy in the development of new antifungal drugs.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
© 2016 The Authors
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/content/journal/micro/10.1099/mic.0.000222
2016-02-01
2024-04-25
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Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex
Microbiology 162, 309 (2016); https://doi.org/10.1099/mic.0.000222
/content/journal/micro/10.1099/mic.0.000222
/content/journal/micro/10.1099/mic.0.000222
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