title: Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species.
abstract: The antifungal activity of some statins against different fungal species has been reported. Thus, at the first moment, the in vitro antifungal activity of simvastatin, atorvastatin and pravastatin was tested against Candida spp. and Cryptococcus spp. Then, in a second approach, considering that the best results were obtained for simvastatin, this drug was evaluated in combination with antifungal drugs against planktonic growth and tested against biofilms of Candida spp. and Cryptococcus spp. Drug susceptibility testing was performed using the microdilution broth method, as described by the Clinical and Laboratory Standards Institute. The interaction between simvastatin and antifungals against planktonic cells was analyzed by calculating the fractional inhibitory concentration index. Regarding biofilm susceptibility, simvastatin was tested against growing biofilm and mature biofilm of one strain of each tested yeast species. Simvastatin showed inhibitory effect against Candida spp. and Cryptococcus spp. with minimum inhibitory concentration values ranging from 15.6 to 1000 mg L(-1) and from 62.5 to 1000 mg L(-1), respectively. The combination of simvastatin with itraconazole and fluconazole showed synergism against Candida spp. and Cryptococcus spp., while the combination of simvastatin with amphotericin B was synergistic only against Cryptococcus spp. Concerning the biofilm assays, simvastatin was able to inhibit both growing biofilm and mature biofilm of Candida spp. and Cryptococcus spp. The present study showed that simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species.
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil. Electronic address: brilhante@ufc.br.
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Erica Pacheco de
authors.initials: EP
authors.lastname: Caetano
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Jonathas Sales
authors.initials: JS
authors.lastname: Oliveira
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Débora de Souza Collares Maia
authors.initials: Dde S
authors.lastname: Castelo-Branco
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Elizabeth Ribeiro Yokobatake
authors.initials: ER
authors.lastname: Souza
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Lucas Pereira de
authors.initials: LP
authors.lastname: Alencar
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Rossana de Aguiar
authors.initials: Rde A
authors.lastname: Cordeiro
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Tereza de Jesus Pinheiro Gomes
authors.initials: Tde J
authors.lastname: Bandeira
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
authors.affiliation: Centro Especializado em Micologia Médica, Programa de Pós-Graduação em Microbiologia Médica, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Programa de Pós-Graduação em Ciências Veterinárias, Universidade Estadual do Ceará (UECE), Fortaleza, CE, Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D003454:Cryptococcus / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D019821:Simvastatin
keywords: Antifungal activity; Biofilm; Candida; Cryptococcus; Simvastatin