title: Reversal of fluconazole resistance induced by a synergistic effect with Acca sellowiana in Candida glabrata strains.
abstract: BACKGROUND
  The increased incidence of non-albicans Candida (NAC) resistant to fluconazole (FLZ) makes it necessary to use new therapeutic alternatives. Acca sellowiana (O.berg) Burret (Myrtaceae) is a guava with several proven biological activities. The interaction with fluconazole can be a feasible alternative to overcome this resistance.
  
  
  OBJECTIVE
  This study evaluates the in vitro antifungal activity of fractions obtained from the lyophilized aqueous extract of the leaves of A. sellowiana against resistant strains of NAC.
  
  
  METHODS
  The antifungal activity of the fractions was evaluated at 500 μg/mL by microdilution method. Checkerboard assay was performed to determine the effect of the combination of the F2 fraction and antifungal at concentrations: MIC/4, MIC/2, MIC, MIC × 2 and MIC × 4.
  
  
  RESULTS
  Candida glabrata showed the lowest MIC values (500-3.90 μg/mL) and the F2 active fraction was the most effective. The association of F2 with FLZ showed a strong synergistic effect (FICI ≤ 0.5) against 100% of C. glabrata resistant isolates. Moreover, the F2 active fraction has demonstrated that probably acts in the cell wall of these yeasts. There was no observed acute dermal toxicity of lyophilized aqueous extract of leaves of A. sellowiana on pig ear skin cells.
  
  
  CONCLUSIONS
  The interaction between substances present in the F2 active fraction is possibly responsible for the antifungal activity presented by this fraction. This study is unprecedented and suggests that the combination of F2 active fraction and FLZ might be used as an alternative treatment for mucocutaneus infections caused by C. glabrata resistant.
authors.affiliation: a Programa de Pós Graduação em Microbiologia Agrícola e do Ambiente , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Gabriella da
authors.initials: GD
authors.lastname: R M Machado
authors.affiliation: a Programa de Pós Graduação em Microbiologia Agrícola e do Ambiente , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Pippi
authors.affiliation: b Programa de Pós Graduação em Ciências Farmacêuticas , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Daiane Flores
authors.initials: DF
authors.lastname: Dalla Lana
authors.affiliation: c Departamento de Farmacociências, Curso de Farmácia , Universidade Federal de Ciências da Saúde de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Ana Paula S
authors.initials: AP
authors.lastname: Amaral
authors.affiliation: d Laboratório de Farmacologia, Instituto Federal Catarinense, Campus Concórdia , Concórdia , Brazil.
authors.forename: Mário Lettieri
authors.initials: ML
authors.lastname: Teixeira
authors.affiliation: c Departamento de Farmacociências, Curso de Farmácia , Universidade Federal de Ciências da Saúde de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Kellen C B de
authors.initials: KC
authors.lastname: Souza
authors.affiliation: a Programa de Pós Graduação em Microbiologia Agrícola e do Ambiente , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|b Programa de Pós Graduação em Ciências Farmacêuticas , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Fuentefria
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D031647:Psidium / Q000737:chemistry; D013552:Swine
chemical_list: D000935:Antifungal Agents; D010936:Plant Extracts; D015725:Fluconazole
keywords: Antifungal agent; Myrtaceae; non-albicans Candida; synergism