RT Journal Article SR Electronic(1) A1 Cordeiro, Rossana de Aguiar A1 Evangelista, Antonio José de Jesus A1 Serpa, Rosana A1 Marques, Francisca Jakelyne de Farias A1 Melo, Charlline Vládia Silva de A1 Oliveira, Jonathas Sales de A1 Franco, Jônatas da Silva A1 Alencar, Lucas Pereira de A1 Bandeira, Tereza de Jesus Pinheiro Gomes A1 Brilhante, Raimunda Sâmia Nogueira A1 Sidrim, José Júlio Costa A1 Rocha, Marcos Fébio GadelhaYR 2016 T1 Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex JF Microbiology, VO 162 IS 2 SP 309 OP 317 DO https://doi.org/10.1099/mic.0.000222 PB Microbiology Society, SN 1465-2080, AB 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 Cryptococcus neoformans/Cryptococcus gattii species complex – agents of the most common life-threatening fungal infection amongst immunocompromised patients. The influence of Hsp90 inhibition was investigated regarding in vitro susceptibility to antifungal agents of planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production of virulence factors in vitro, and experimental infection in Caenorhabditis elegans. Hsp90 inhibition inhibited the in vitro growth of planktonic cells of Cryptococcus spp. at concentrations ranging from 0.5 to 2 μg ml− 1 and increased the in vitro inhibitory effect of azoles, especially fluconazole (FLC) (P < 0.05). Inhibition of Hsp90 also increased the antifungal activity of azoles against biofilm formation and mature biofilms of Cryptococcus spp., notably for Cryptococcus gattii. Furthermore, Hsp90 inhibition compromised the permeability of the cell membrane, and reduced planktonic growth at 37 °C and the capsular size of Cryptococcus spp. In addition, Hsp90 inhibition enhanced the antifungal activity of FLC during experimental infection using Caenorhabditis elegans. Therefore, our results indicate that Hsp90 inhibition can be an important strategy in the development of new antifungal drugs., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000222