Azole resistance in Candida albicans from animals: Highlights on efflux pump activity and gene overexpression

• Published in: Mycoses Vol. 60; no. 7; pp. 462 - 468
• Main Authors: Rocha, Marcos Fábio Gadelha, Bandeira, Silviane Praciano, Alencar, Lucas Pereira, Melo, Luciana Magalhães, Sales, Jamille Alencar, Paiva, Manoel de Araújo Neto, Teixeira, Carlos Eduardo Cordeiro, Castelo‐Branco, Débora de Souza Collares Maia, Pereira‐Neto, Waldemiro de Aquino, Cordeiro, Rossana de Aguiar, Sidrim, José Júlio Costa, Brilhante, Raimunda Sâmia Nogueira
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-07-2017
• Subjects: animal; Animals; antifungal; Antifungal Agents - pharmacology; Azoles - pharmacology; Biological Transport, Active; Candida albicans - chemistry; Candida albicans - drug effects; Candida albicans - genetics; Candida albicans - isolation & purification; Candidiasis - microbiology; Candidiasis - veterinary; Carrier State - microbiology; Carrier State - veterinary; Complementarity-determining region 1; Drug Resistance, Fungal; Ergosterol; Ergosterol - analysis; Fluconazole; Gene Expression; Gene Expression Profiling; Itraconazole; MDR1 protein; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Potassium; Real-Time Polymerase Chain Reaction; resistance; Rhodamine 6G; yeast; antifungal; animal; gene expression; resistance; yeast
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.12611

Summary
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.