title: Farnesol inhibits in vitro growth of the Cryptococcus neoformans species complex with no significant changes in virulence-related exoenzymes.
abstract: Farnesol is a sesquiterpene alcohol that modulates cell-to-cell communication in Candida albicans. In recent years, several studies have shown that this molecule presents inhibitory effects against non-albicans Candida species, Paracoccidioides brasiliensis and bacteria. The present study aimed at determining the effect of farnesol on the growth of strains of the Cryptococcus neoformans species complex, through microdilution assays. In addition, the effect of farnesol on the synthesis of phospholipase and protease - important virulence-associated enzymes - by C. neoformans and Cryptococcus gattii was also investigated. A total of 36 strains were studied, out of which 20 were from veterinary sources, 8 were from human cases and 8 were from a reference collection. The minimum inhibitory concentrations (MICs) were determined in accordance with the M27-A3 protocol as described by the CLSI and farnesol was tested at a concentration range of 0.29-150 μM. Phospholipase and protease activities were evaluated through growth on egg yolk agar and spectrophotometry, respectively, after pre-incubating the strains at different farnesol concentrations (MIC/4, MIC/2 and MIC). It was observed that farnesol presents an inhibitory activity against C. neoformans and C. gattii (MIC range: 0.29-75.0 μM). Although farnesol did not significantly alter phospholipase activity, a tendency to decrease this activity was observed. Concerning protease, no statistically significant differences were observed when comparing the production before and after pre-incubation at different farnesol concentrations. Based on these findings, it can be concluded that farnesol has in vitro inhibitory activity against C. neoformans and C. gattii, but has little impact on the production of the analyzed virulence factors.
authors.affiliation: Department of Pathology and Legal Medicine, School of Medicine, Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Rossana de Aguiar
authors.initials: Rde A
authors.lastname: Cordeiro
authors.forename: George Cândido
authors.initials: GC
authors.lastname: Nogueira
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.forename: Carlos Eduardo Cordeiro
authors.initials: CE
authors.lastname: Teixeira
authors.forename: Charles Ielpo
authors.initials: CI
authors.lastname: Mourão
authors.forename: Débora de Souza Collares Maia
authors.initials: Dde S
authors.lastname: Castelo-Branco
authors.forename: Manoel de Araújo Neto
authors.initials: Mde A
authors.lastname: Paiva
authors.forename: Joyce Fonteles
authors.initials: JF
authors.lastname: Ribeiro
authors.forename: André Jalles
authors.initials: AJ
authors.lastname: Monteiro
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
mesh_terms: D000818:Animals; D010856:Columbidae; D003453:Cryptococcosis / Q000201:enzymology / Q000382:microbiology* / Q000662:veterinary*; D056285:Cryptococcus gattii / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D005204:Farnesol / Q000494:pharmacology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010447:Peptide Hydrolases / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D005204:Farnesol; D010740:Phospholipases; D010447:Peptide Hydrolases