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Investigation of Erg11 Gene Expression Among Fluconazole-Resistant Candida Albicans: First Report From an Iranian Referral Paediatric Hospital Publisher Pubmed



Teymuri M1, 2 ; Mamishi S2, 3 ; Pourakbari B2 ; Mahmoudi S2 ; Ashtiani MT4 ; Sadeghi RH2 ; Yadegari MH1, 5
Authors
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Authors Affiliations
  1. 1. Department of Medical Mycology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Infectious Diseases, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: British Journal of Biomedical Science Published:2015


Abstract

The multiplicity of mechanisms of resistance to azole antifungal agents has been described. As fluconazoleresistant clinical Candida albicans isolates that constitutively over-express ERG11 have been identified in previous studies, the aim of this study is to investigate this molecular mechanism involved in fluconazole resistance of C. albicans clinical isolates. Fluconazole susceptibility testing was carried out on clinical isolates of Candida spp. obtained from hospitalised children in an Iranian referral children's hospital. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique was used to differentiate Candida spp. The resistant C. albicans isolates were subjected to RT-qPCR using primers that identify ERG11 gene expression. Of the 142 Candida spp. isolates studied, C. albicans was the most predominant isolate, occurring in 68.3% (97/142) of the patients. According to the CLSI method, the majority of the C. albicans isolates (91.7%, 89/97), categorised as susceptible (minimum inhibitory concentration [MIC] ≥8 μg/mL), five isolates were considered resistant (MIC ≤64 μg/mL) and three had dose-dependent susceptibility (MIC=8.16-32 μg/mL). The ERG11 gene in the five fluconazole-resistant C. albicans isolates was upregulated 4.15-5.84-fold relative to the ATCC 10231 control strain. In this study, the expression of ERG11 was upregulated in all the fluconazole-resistant C. albicans isolates. There are limited data on the antifungal susceptibility of Candida spp. as well as the molecular mechanism of azole resistance in Iran, especially for isolates causing infections in children. Therefore, the surveillance of antifungal resistance patterns and investigation of other mechanisms of azole resistance in all Candida spp. isolates is recommended.
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