Pourakbari Babak, Teymuri Mostafa, Mahmoudi Shima, Valian Sepideh K, Movahedi Zahra, Eshaghi Hamid, Mamishi Setareh
Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran. Iran.
Department of Mycology, Faculty of Medicine, Tarbiat Modares University, Tehran. Iran.
Infect Disord Drug Targets. 2017;17(3):178-184. doi: 10.2174/1871526517666170531114335.
Resistance to azole antifungals is considered as a significant problem in Candida albicans infections. Several molecular mechanisms of fluconazole resistance including alterations in the gene encoding the target enzyme ERG11 or overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 have been reported. The aim of this study was to investigate overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 in fluconazole- resistant C. albicans.
In this study, a total of 97 clinical isolates of C. albicans were isolated from hospitalized children in Children medical center, an Iranian referral hospital. Fluconazole susceptibility testing of C. albicans was performed using the broth microdilution method according to the CLSI guideline. Expression of CDR1, CDR2, MDR1, MDR2 and FLU1 genes was measured using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and 18SrRNA gene was used as a housekeeping gene.
Among 97 C. albicans isolates, 5 strains were categorized as fluconazoleresistant. Overexpression of CDR1, CDR2 and MDR2 genes was found in all isolates. MDR1 overexpression was observed in four resistant isolates. None of the resistant strains displayed increases in FLU1 transcript levels.
Overexpression of the CDR1, CDR2, MDR1 and MDR2 genes might play an important role in fluconazole-resistant C. albicans. No link between expression of FLU1 and fluconazole resistance was found.
对唑类抗真菌药的耐药性被认为是白色念珠菌感染中的一个重大问题。已报道了几种氟康唑耐药的分子机制,包括编码靶酶ERG11的基因改变或外排泵基因(包括CDR1、CDR2、MDR1、MDR2和FLU1)的过表达。本研究的目的是调查耐氟康唑的白色念珠菌中外排泵基因(包括CDR1、CDR2、MDR1、MDR2和FLU1)的过表达情况。
在本研究中,从伊朗一家转诊医院儿童医学中心的住院儿童中分离出97株白色念珠菌临床分离株。根据CLSI指南,采用肉汤微量稀释法对白色念珠菌进行氟康唑敏感性测试。使用定量实时逆转录聚合酶链反应(RT-PCR)测量CDR1、CDR2、MDR1、MDR2和FLU1基因的表达,并将18SrRNA基因用作管家基因。
在97株白色念珠菌分离株中,5株被归类为耐氟康唑。在所有分离株中均发现CDR1、CDR2和MDR2基因过表达。在4株耐药分离株中观察到MDR1过表达。没有一株耐药菌株的FLU1转录水平升高。
CDR1、CDR2、MDR1和MDR2基因的过表达可能在耐氟康唑的白色念珠菌中起重要作用。未发现FLU1表达与氟康唑耐药之间的联系。