Pinto Ana Carolina C, Rocha Debora A S, Moraes Daniel C DE, Junqueira Maria L, Ferreira-Pereira Antonio
Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I, Sala 44, Ilha do Fundão, 21949-902 Rio de Janeiro, RJ, Brazil.
Hospital Universitário, Universidade Federal de Juiz de Fora, Rua Catulo Breviglieri, s/n, Santa Catarina, 36036-110 Juiz de Fora, MG, Brazil.
An Acad Bras Cienc. 2019 Jul 29;91(3):e20180654. doi: 10.1590/0001-3765201920180654.
Candida albicans is the most frequent fungal species that causes infections in humans. Fluconazole is the main antifungal used to treat Candida infections, and its prolonged and indiscriminate use for the last decades are the most established causes which originated resistant strains. Fungal drug resistance is associated to alterations in ERG11 gene and overexpression of multidrug resistance (MDR) transporters belonging to two families: ATP-binding cassette (ABC) and Major Facilitator Superfamily (MFS). To evaluate the role of MFS transporters in azoles resistance of C. albicans clinical strains, this study aimed to analyze four Candida albicans clinical isolates from the University Hospital in Juiz de Fora (Minas Gerais/Brazil), selected in our previous study as they were unaffected by FK506, an ABC pumps inhibitor. In a primary investigation on MFS proteins overexpression, the extrusion of fluorescent substrates (rhodamine 6G and nile red) was analyzed by fluorescence microscopy and flow cytometry. Results suggest participation of MFS transporters in azole resistance of C. albicans isolates and indicate the existence of secondary resistance mechanisms. Therefore, this study contributes to the information about Candida albicans infections in Brazil and reinforces the importance of epidemiological studies focusing on an improved understanding of the disease and further resistance reversion.
白色念珠菌是引起人类感染最常见的真菌物种。氟康唑是用于治疗念珠菌感染的主要抗真菌药物，在过去几十年中其长期和不加区分的使用是产生耐药菌株最确定的原因。真菌耐药性与ERG11基因的改变以及属于两个家族的多药耐药（MDR）转运蛋白的过表达有关：ATP结合盒（ABC）和主要易化子超家族（MFS）。为了评估MFS转运蛋白在白色念珠菌临床菌株唑类耐药性中的作用，本研究旨在分析来自巴西米纳斯吉拉斯州茹伊斯迪福拉大学医院的四株白色念珠菌临床分离株，这些分离株在我们之前的研究中被选中，因为它们不受ABC泵抑制剂FK506的影响。在对MFS蛋白过表达的初步研究中，通过荧光显微镜和流式细胞术分析了荧光底物（罗丹明6G和尼罗红）的外排情况。结果表明MFS转运蛋白参与了白色念珠菌分离株的唑类耐药性，并表明存在二级耐药机制。因此，本研究为巴西白色念珠菌感染的相关信息做出了贡献，并强化了流行病学研究的重要性，这些研究专注于更好地理解该疾病以及进一步逆转耐药性。
