title: Histoplasma capsulatum in planktonic and biofilm forms: in vitro susceptibility to amphotericin B, itraconazole and farnesol.
abstract: It is believed that most microbial infections are caused by pathogens organized in biofilms. Recently, it was shown that the dimorphic fungus Histoplasma capsulatum, estimated to be the most common cause of fungal respiratory diseases, is also able to form biofilm. Although the antifungal therapy commonly used is effective, refractory cases and recurrences have been reported. In the search for new compounds with antimicrobial activity, the sesquiterpene farnesol has gained prominence for its antifungal action. This study aimed to evaluate the in vitro susceptibility of H. capsulatum var. capsulatum to the antifungal agents itraconazole and amphotericin B, and farnesol alone and combined, as well as to determine the in vitro antifungal activity of these compounds against biofilms of this pathogen. The results show that farnesol has antifungal activity against H. capsulatum in the yeast and filamentous phases, with MIC values ranging from 0.0078 to 0.00312 µM. A synergistic effect (fractional inhibitory concentration index ≤0.5) between itraconazole and farnesol was found against 100 and 83.3 % of the isolates in yeast and mycelial forms, respectively, while synergism between amphotericin B and farnesol was only observed against 37.5 and 44.4 % of the isolates in yeast and filamentous forms, respectively. Afterwards, the antifungal drugs, itraconazole and amphotericin B, and farnesol alone, and the combination of itraconazole and farnesol, were tested against mature biofilms of H. capsulatum, through XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) metabolic assay, and the itraconazole and amphotericin B showed lower antibiofilm activity when compared to farnesol alone and farnesol combined with itraconazole. In conclusion, farnesol showed promising results as an antifungal agent against H. capsulatum and also showed adjuvant action, especially when combined with itraconazole, increasing the fungal susceptibility to this drug.
authors: Federal University of Ceará, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Raimunda Sâmia Nogueira
authors: RSN
authors: Brilhante
authors: Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Rita Amanda Chaves
authors: RAC
authors: de Lima
authors: Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Francisca Jakelyne de Farias
authors: FJF
authors: Marques
authors: Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Natalya Fechine
authors: NF
authors: Silva
authors: Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Érica Pacheco
authors: ÉP
authors: Caetano
authors: Federal University of Ceará, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Débora de Souza Collares Maia
authors: DSCM
authors: Castelo-Branco
authors: School of Medicine, Christus College, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Tereza de Jesus Pinheiro Gomes
authors: TJPG
authors: Bandeira
authors: Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: José Luciano Bezerra
authors: JLB
authors: Moreira
authors: Federal University of Ceará, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Rossana de Aguiar
authors: RA
authors: Cordeiro
authors: Department of Statistics and Applied Mathematics, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: André Jalles
authors: AJ
authors: Monteiro
authors: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, Brazil.
authors: Zoilo Pires de
authors: ZP
authors: Camargo
authors: Federal University of Ceará, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: José Júlio Costa
authors: JJC
authors: Sidrim
authors: State University of Ceará, Fortaleza, Ceará, Brazil.|Specialized Medical Mycology Center (CEMM), Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors: Marcos Fábio Gadelha
authors: MFG
authors: Rocha
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004357:Drug Synergism; D005204:Farnesol / Q000494:pharmacology*; D006658:Histoplasma / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D005204:Farnesol; D000666:Amphotericin B