@article{mbs:/content/journal/micro/10.1099/mic.0.000222, author = "Cordeiro, Rossana de Aguiar and Evangelista, Antonio José de Jesus and Serpa, Rosana and Marques, Francisca Jakelyne de Farias and Melo, Charlline Vládia Silva de and Oliveira, Jonathas Sales de and Franco, Jônatas da Silva and Alencar, Lucas Pereira de and Bandeira, Tereza de Jesus Pinheiro Gomes and Brilhante, Raimunda Sâmia Nogueira and Sidrim, José Júlio Costa and Rocha, Marcos Fébio Gadelha", title = "Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex", journal= "Microbiology", year = "2016", volume = "162", number = "2", pages = "309-317", doi = "https://doi.org/10.1099/mic.0.000222", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000222", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", 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 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.", }