Rocha Marcos Fábio Gadelha, Bandeira Silviane Praciano, de 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
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.
Mycoses. 2017 Jul;60(7):462-468. doi: 10.1111/myc.12611. Epub 2017 Mar 10.
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.
本研究调查了动物源白色念珠菌对唑类耐药的潜在机制，包括外排泵活性、麦角甾醇含量和基因表达。为此，根据M27-A3文件，对30株动物源唑类耐药白色念珠菌菌株进行了抗真菌药敏试验，通过罗丹明6G试验检测外排泵活性，通过RT-qPCR检测麦角甾醇含量以及CDR1、CDR2、MDR1、ERG11基因的表达。这些菌株对至少一种唑类衍生物耐药。分别在23株和26株菌株中检测到对氟康唑和伊曲康唑的耐药性。罗丹明6G试验显示耐药菌株中外排泵活性增加，这表明可能存在耐药机制。即使在氟康唑暴露后，耐药菌株和敏感菌株之间的麦角甾醇含量也没有差异。在30株菌株中，22株（73.3%）动物耐药菌株过度表达了一个或多个基因。在这一组中，40.9%（9/22）过度表达CDR1，18.2%（4/22）过度表达CDR2，59.1%（13/22）过度表达MDR1，54.5%（12/22）过度表达ERG11。关于基因表达，仅在CDR1和CDR2之间观察到正相关。因此，动物源白色念珠菌菌株中的唑类耐药是一个多因素过程，涉及外排泵活性增加和不同基因的过度表达。
