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Assessment of antifungal resistance and associated molecular mechanism in Candida albicans isolates from different cohorts of patients in North Indian state of Haryana.
Folia Microbiologica ( IF 2.6 ) Pub Date : 2020-03-26 , DOI: 10.1007/s12223-020-00785-6
Ashok Kumar 1 , Remya Nair 1 , Mohit Kumar 1, 2 , Atanu Banerjee 1 , Arunaloke Chakrabarti 3 , Shivaprakash M Rudramurthy 3 , Ruchika Bagga 4 , Naseem A Gaur 2 , Alok K Mondal 5 , Rajendra Prasad 1
Affiliation  

The present study examines the trend in distribution of Candida species and their antifungal resistance patterns in hospitals across Haryana, a North Indian state with poorly addressed epidemiology of fungal infections. In our collection of 228 Candida isolates, Candida albicans dominated in both high vaginal swab (HVS) and urine samples while Candida glabrata and Candida tropicalis were the second-highest non-albicans Candida species (NAC), respectively. Of note, in blood samples, C. tropicalis and C. albicans were present in equal numbers. All 228 isolates were subjected to antifungal susceptibility tests, whereby 51% of C. albicans recovered from HVS samples displayed fluconazole resistance. To understand its mechanistic basis, expression profiling of efflux pump genes CDR1, CDR2, MDR1 and azole drug target, ERG11 was performed in 20 randomly selected resistant isolates, wherein many isolates elicited higher expression. Further, ERG11 gene sequencing suggested that most of the isolates harbored mutations, which are not reported with azole resistance. However, one isolate, RPCA9 (MIC 64 μg/mL) harbored triple mutation (Y132C, F145L, A114V), wherein Y132 and F145 sites were previously implicated in azole resistance. Interestingly, one isolate, (RPCA61) having MIC > 128 μg/mL harbored a novel mutation, G129R. Of note, HVS isolates RPCA 21, RPCA 22, and RPCA 44 (MICs 64 to > 128 μg/mL) did not show any change in alteration in ERG11 or overexpression of efflux pump genes. Together, this study presents a first report of Candida infections in selected hospitals of Haryana State.



中文翻译:

在印度北部哈里亚纳邦不同人群的白色念珠菌分离株中抗真菌耐药性及其相关分子机制的评估。

本研究调查了北印度州哈里亚纳邦的医院中念珠菌种类的分布趋势及其抗真菌耐药性模式,该邦是印度北部真菌感染流行病学研究欠佳的州。在我们的228集念珠菌株,白色念珠菌在高阴道拭子(HVS)和尿液样本为主,同时光滑念珠菌热带念珠菌,是第二高的非白色念珠菌念珠菌种(NAC),分别。值得注意的是,在血液样本中,热带念珠菌白色念珠菌的数量相等。所有228株分离物均经过抗真菌药敏试验,其中51%白色念珠菌从HVS样品中回收的氟康唑具有抗药性。为了解其机制基础,外排泵基因CDR1,CDR2,MDR1和唑类药物靶标ERG11的表达谱分析在20个随机选择的耐药菌株中进行,其中许多菌株引起更高的表达。此外,ERG11基因测序表明,大多数分离株均具有突变,但尚无唑抗性报道。但是,一种分离株RPCA9(MIC 64μg/ mL)具有三重突变(Y132C,F145L,A114V),其中Y132和F145位点先前与吡咯抗性有关。有趣的是,一种MIC(MIC> 128μg/ mL)的分离株(RPCA61)含有一个新的突变G129R。值得注意的是,HVS分离株RPCA 21,RPCA 22和RPCA 44(MIC 64至> 128μg/ mL)未显示ERG11改变或外排泵基因过表达的任何变化。哈里亚纳邦部分医院的念珠菌感染。

更新日期:2020-03-26
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