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临床耐药中念珠菌的外排ATP酶和反向转运蛋白

Candida Efflux ATPases and Antiporters in Clinical Drug Resistance.

作者信息

Prasad Rajendra, Rawal Manpreet Kaur, Shah Abdul Haseeb

机构信息

Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

AMITY Institute of Integrative Sciences and Health (AIISH), Amity University Haryana, Manesar, Gurgaon, Haryana, India.

出版信息

Adv Exp Med Biol. 2016;892:351-376. doi: 10.1007/978-3-319-25304-6_15.

Abstract

An enhanced expression of genes encoding ATP binding cassette (ABC) and major facilitator superfamily (MFS) transport proteins are known to contribute to the development of tolerance to antifungals in pathogenic yeasts. For example, the azole resistant (AR) clinical isolates of the opportunistic human fungal pathogen Candida albicans show an overexpression of CDR1 and/or CaMDR1 belonging to ABC and MFS, superfamilies, respectively. The reduced accumulation (due to rapid efflux) of drugs in AR isolates confirms the role of efflux pump proteins in the development of drug tolerance. Considering the importance of major multidrug transporters, the focus of recent research has been to understand the structure and function of these proteins which could help to design inhibitors/modulators of these pump proteins. This chapter focuses on some aspects of the structure and function of yeast transporter proteins particularly in relation to MDR in Candida.

摘要

已知编码ATP结合盒(ABC)和主要易化子超家族(MFS)转运蛋白的基因表达增强有助于致病性酵母产生抗真菌耐受性。例如,机会性人类真菌病原体白色念珠菌的唑类耐药(AR)临床分离株分别显示出属于ABC和MFS超家族的CDR1和/或CaMDR1的过表达。AR分离株中药物积累减少(由于快速外排)证实了外排泵蛋白在耐药性发展中的作用。考虑到主要多药转运蛋白的重要性,最近的研究重点是了解这些蛋白的结构和功能,这有助于设计这些泵蛋白的抑制剂/调节剂。本章重点介绍酵母转运蛋白结构和功能的一些方面,特别是与念珠菌多药耐药相关的方面。

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