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

• DOI: 10.1099/mic.0.000222
• Publication Date: 2015-12-09T05:53:12Z
• Authors: Rossana de Aguiar...; Antonio José de J...; Rosana Serpa; Francisca Jakelyn...; Charlline Vládia ...; Jonathas Sales de...; Jônatas da Silva ...; Lucas Pereira de ...; Tereza de Jesus P...; Raimunda Sâmia No...; José Júlio Costa ...; Marcos Fébio Gade...
• Keywords: Cryptococcus gattii; Growth inhibition

Heat-shock proteins (Hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role infectious process. This study investigated effect pharmacological inhibition Hsp90 by radicicol on Cryptococcus neoformans/Cryptococcus gattii species complex--agents most common life-threatening infection amongst immunocompromised patients. The influence was regarding vitro susceptibility to antifungal agents planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production virulence factors vitro, experimental Caenorhabditis elegans. inhibited cells spp. concentrations ranging from 0.5 2 μg ml(-1) increased inhibitory azoles, especially fluconazole (FLC) (P < 0.05). Inhibition also activity azoles against biofilm formation mature biofilms spp., notably gattii. Furthermore, compromised permeability membrane, reduced °C capsular size In addition, enhanced FLC during using Therefore, our results indicate that can be strategy development new drugs.