title: Inhibitory activity of isoniazid and ethionamide against Cryptococcus biofilms.
abstract: In recent years, the search for drugs to treat systemic and opportunistic mycoses has attracted great interest from the scientific community. This study evaluated the in vitro inhibitory effect of the antituberculosis drugs isoniazid and ethionamide alone and combined with itraconazole and fluconazole against biofilms of Cryptococcus neoformans and Cryptococcus gattii. Antimicrobials were tested at defined concentrations after susceptibility assays with Cryptococcus planktonic cells. In addition, we investigated the synergistic interaction of antituberculosis drugs and azole derivatives against Cryptococcus planktonic cells, as well as the influence of isoniazid and ethionamide on ergosterol content and cell membrane permeability. Isoniazid and ethionamide inhibited both biofilm formation and viability of mature biofilms. Combinations formed by antituberculosis drugs and azoles proved synergic against both planktonic and sessile cells, showing an ability to reduce Cryptococcus biofilms by approximately 50%. Furthermore, isoniazid and ethionamide reduced the content of ergosterol in Cryptococcus spp. planktonic cells and destabilized or permeabilized the fungal cell membrane, leading to leakage of macromolecules. Owing to the paucity of drugs able to inhibit Cryptococcus biofilms, we believe that the results presented here might be of interest in the designing of new antifungal compounds.
authors.affiliation: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.|b 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: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Serpa
authors.affiliation: a 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: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Charlline Vládia Silva
authors.initials: CV
authors.lastname: de Melo
authors.affiliation: b Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Antonio José de Jesus
authors.initials: AJ
authors.lastname: Evangelista
authors.affiliation: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Valquíria Ferreira
authors.initials: VF
authors.lastname: Mota
authors.affiliation: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.|b Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.affiliation: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.|c 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: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.|d Postgraduate Program in Veterinary Science, State University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
authors.affiliation: a Postgraduate Program in Medical Microbiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.|b Postgraduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002463:Cell Membrane Permeability; D056285:Cryptococcus gattii / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004875:Ergosterol / Q000737:chemistry; D005000:Ethionamide / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole; D005000:Ethionamide; D007538:Isoniazid; D004875:Ergosterol
keywords: Cryptococcus spp.; biofilms; ethionamide; isoniazid; isoniazide; synergie; synergism; éthionamide