Overexpression of Both ERG11 and ABC2 Genes Might Be Responsible for Itraconazole Resistance in Clinical Isolates of Candida krusei

作者: Xiaoyuan He , Mingfeng Zhao , Jinyan Chen , Rimao Wu , Jianlei Zhang

DOI: 10.1371/JOURNAL.PONE.0136185

关键词:

摘要: Objective To study the main molecular mechanisms responsible for itraconazole resistance in clinical isolates of Candida krusei. Methods The 14α-demethylases encoded by ERG11 gene 16 C.krusei were amplified polymerase chain reaction (PCR), and their nucleotide sequences determined to detect point mutations. Meanwhile, efflux transporters (ABC1 ABC2) genes quantitative real-time reverse transcription (qRT-PCR) expression itraconazole-resistant (R), itraconazole-susceptible dose dependent (SDD) (S) at mRNA level. Results We found 7-point mutations all isolates, including 6 synonymous 1 missense mutation (C44T). However, was three groups. The levels showed higher compared with ones (P = 0.015 P 0.002 respectively). ABC2 group significantly than other two groups, appeared increase decrease susceptibility 0.007 SDD S, 0.016 R, P<0.001 S R While ABC1 presented lower resistant strains. ERG11, a (CK10) both voriconazole expressed highest isolates. Conclusions There are polymorphisms C.krusei. may not be involved development overexpression might acquired these isolates.

参考文章(23)
K Venkateswarlu, D W Denning, N J Manning, S L Kelly, Reduced accumulation of drug in Candida krusei accounts for itraconazole resistance. Antimicrobial Agents and Chemotherapy. ,vol. 40, pp. 2443- 2446 ,(1996) , 10.1128/AAC.40.11.2443
A. L. Barry, M. A. Pfaller, S. D. Brown, A. Espinel-Ingroff, M. A. Ghannoum, C. Knapp, R. P. Rennie, J. H. Rex, M. G. Rinaldi, Quality Control Limits for Broth Microdilution Susceptibility Tests of Ten Antifungal Agents Journal of Clinical Microbiology. ,vol. 38, pp. 3457- 3459 ,(2000) , 10.1128/JCM.38.9.3457-3459.2000
R Raoofian, M Safara, F Zaini, M Heidari, M Tavakoli, M Kordbacheh, Upregulation of the ERG11 gene in Candida krusei by azoles. Tehran University of Medical Sciences. ,vol. 18, pp. 276- 280 ,(2010)
Sónia Silva, Melyssa Negri, Mariana Henriques, Rosário Oliveira, David W. Williams, Joana Azeredo, Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance Fems Microbiology Reviews. ,vol. 36, pp. 288- 305 ,(2012) , 10.1111/J.1574-6976.2011.00278.X
Małgorzata Bondaryk, Wiesław Kurzątkowski, Monika Staniszewska, Antifungal agents commonly used in the superficial and mucosal candidiasis treatment: mode of action and resistance development Advances in Dermatology and Allergology. ,vol. 5, pp. 293- 301 ,(2013) , 10.5114/PDIA.2013.38358
LM Chen, YH Xu, CL Zhou, J Zhao, CY Li, R Wang, None, Overexpression of CDR1 and CDR2 Genes Plays an Important Role in Fluconazole Resistance in Candida albicans with G487T and T916C Mutations Journal of International Medical Research. ,vol. 38, pp. 536- 545 ,(2010) , 10.1177/147323001003800216
Wanda Cornistein, Andrea Mora, Nora Orellana, Federico Javier Capparelli, Marcelo del Castillo, Candida: epidemiología y factores de riesgo para especies no albicans Enfermedades Infecciosas Y Microbiologia Clinica. ,vol. 31, pp. 380- 384 ,(2013) , 10.1016/J.EIMC.2012.09.011
Elisabete Ricardo, Isabel M. Miranda, Isabel Faria-Ramos, Raquel M. Silva, Acácio Gonçalves Rodrigues, Cidália Pina-Vaz, In Vivo and In Vitro Acquisition of Resistance to Voriconazole by Candida krusei Antimicrobial Agents and Chemotherapy. ,vol. 58, pp. 4604- 4611 ,(2014) , 10.1128/AAC.02603-14