title: In vitro inhibitory activity of terpenic derivatives against clinical and environmental strains of the Sporothrix schenkii complex.
abstract: Sporotrichosis is a subacute or chronic subcutaneous infection, caused by the fungus Sporothrix schenkii complex, occurring in human and animal tissues. Potassium iodide and itraconazole have been used as effective therapy for first-choice treatment, while amphotericin B may be indicated for disseminated infection. However, the adverse effects of potassium iodide and amphotericin B or the long duration of therapy with itraconazole often weigh against their use, leading to the search for alternatives for the treatment of severe infections. Terpinen-4-ol and farnesol are components of essential oils present in many plant species and have been described to have antifungal activity against microorganisms. In this study, 40 strains of Sporothrix spp. were tested for the susceptibility to terpinen-4-ol and farnesol. Changes in cytoplasmic membrane permeability were also investigated. Terpenes inhibited all Sporothrix strains with MIC values ranging from 87.9 to 1,429.8 μg/ml for terpinen-4-ol and from 0.003 to 0.222 μg/ml for farnesol. The MFC values ranged from 177.8 to 5,722.6 μg/ml and from 0.027 to 0.88 μg/ml, respectively, for terpinen-4-ol and farnesol. Farnesol was the most active compound for the Sporothrix strains. Significant loss of 260 and 280 nm-absorbing material did not occur after treatment with concentrations equivalent to the MIC and sub-MIC of the tested terpenes, when compared to corresponding untreated samples. The failure of terpenes to lyse Sporothrix cells suggests that their primary mechanism of action is not by causing irreversible cell membrane damage. Thus, new studies are needed to better understand the mechanisms involved in the antifungal activity.
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil brilhante@ufc.br.
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.affiliation: Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Natalya Fechine
authors.initials: NF
authors.lastname: Silva
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Francisca Jakelyne de Farias
authors.initials: FJ
authors.lastname: Marques
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Débora de Souza Collares Maia
authors.initials: Dde S
authors.lastname: Castelo-Branco
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Rita Amanda Chaves
authors.initials: RA
authors.lastname: de Lima
authors.affiliation: Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Angela Donato Maia
authors.initials: AD
authors.lastname: Malaquias
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Erica Pacheco
authors.initials: EP
authors.lastname: Caetano
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Giovanna Riello
authors.initials: GR
authors.lastname: Barbosa
authors.affiliation: Department of Microbiology, Immunology and Parasitology, São Paulo Federal University, São Paulo, Brazil.
authors.forename: Zoilo Pires
authors.initials: ZP
authors.lastname: de Camargo
authors.affiliation: Department of Microbiology, Immunology and Parasitology, São Paulo Federal University, São Paulo, Brazil.
authors.forename: Anderson Messias
authors.initials: AM
authors.lastname: Rodrigues
authors.affiliation: Department of Statistics and Applied Mathematics, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: André Jalles
authors.initials: AJ
authors.lastname: Monteiro
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil School of Medicine, Christus College, UNICHRISTUS, Fortaleza, Ceará, Brazil.
authors.forename: Tereza de Jesus Pinheiro Gomes
authors.initials: Tde J
authors.lastname: Bandeira
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Rossana de Aguiar
authors.initials: Rde A
authors.lastname: Cordeiro
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: José Luciano Bezerra
authors.initials: JL
authors.lastname: Moreira
authors.affiliation: Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004783:Environmental Microbiology; D005204:Farnesol / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D013175:Sporothrix / Q000187:drug effects* / Q000302:isolation & purification; D013174:Sporotrichosis / Q000382:microbiology*; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D013729:Terpenes; D005204:Farnesol; C034019:terpinenol-4
keywords: Sporothrix spp.; farnesol; terpinen-4-ol