title: Azole resistance in Candida albicans from animals: Highlights on efflux pump activity and gene overexpression.
abstract: This study investigated potential mechanisms of azole resistance among Candida albicans from animals, including efflux pump activity, ergosterol content and gene expression. For this purpose, 30 azole-resistant C. albicans strains from animals were tested for their antifungal susceptibility, according to document M27-A3, efflux pump activity by rhodamine 6G test, ergosterol content and expression of the genes CDR1, CDR2, MDR1, ERG11 by RT-qPCR. These strains were resistant to at least one azole derivative. Resistance to fluconazole and itraconazole was detected in 23 and 26 strains respectively. Rhodamine 6G tests showed increased activity of efflux pumps in the resistant strains, showing a possible resistance mechanism. There was no difference in ergosterol content between resistant and susceptible strains, even after fluconazole exposure. From 30 strains, 22 (73.3%) resistant animal strains overexpressed one or more genes. From this group, 40.9% (9/22) overexpressed CDR1, 18.2% (4/22) overexpressed CDR2, 59.1% (13/22) overexpressed MDR1 and 54.5% (12/22) overexpressed ERG11. Concerning gene expression, a positive correlation was observed only between CDR1 and CDR2. Thus, azole resistance in C. albicans strains from animals is a multifactorial process that involves increased efflux pump activity and the overexpression of different genes.
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.|School of Veterinary Medicine, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Marcos Fábio Gadelha
authors.initials: MFG
authors.lastname: Rocha
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Silviane Praciano
authors.initials: SP
authors.lastname: Bandeira
authors.affiliation: School of Veterinary Medicine, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Lucas Pereira
authors.initials: LP
authors.lastname: de Alencar
authors.affiliation: School of Veterinary Medicine, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Luciana Magalhães
authors.initials: LM
authors.lastname: Melo
authors.affiliation: School of Veterinary Medicine, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Jamille Alencar
authors.initials: JA
authors.lastname: Sales
authors.affiliation: School of Veterinary Medicine, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Manoel de Araújo Neto
authors.initials: MAN
authors.lastname: Paiva
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Carlos Eduardo Cordeiro
authors.initials: CEC
authors.lastname: Teixeira
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Débora de Souza Collares Maia
authors.initials: DSCM
authors.lastname: Castelo-Branco
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Waldemiro de Aquino
authors.initials: WA
authors.lastname: Pereira-Neto
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Rossana de Aguiar
authors.initials: RA
authors.lastname: Cordeiro
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: José Júlio Costa
authors.initials: JJC
authors.lastname: Sidrim
authors.affiliation: Department of Pathology and Legal Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Raimunda Sâmia Nogueira
authors.identifier: http://orcid.org/0000-0002-5102-3582
authors.initials: RSN
authors.lastname: Brilhante
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001693:Biological Transport, Active; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology / Q000662:veterinary; D002353:Carrier State / Q000382:microbiology / Q000662:veterinary; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000032:analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D026901:Membrane Transport Proteins; D004875:Ergosterol
keywords: animal; antifungal; gene expression; resistance; yeast