Preprint Review Version 1 This version is not peer-reviewed

Fungal resistance to echinocandins and the MDR phenomenon in Candida glabrata

Version 1 : Received: 16 August 2018 / Approved: 17 August 2018 / Online: 17 August 2018 (12:43:43 CEST)

A peer-reviewed article of this Preprint also exists.

Healey, K.R.; Perlin, D.S. Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida glabrata. J. Fungi 2018, 4, 105. Healey, K.R.; Perlin, D.S. Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida glabrata. J. Fungi 2018, 4, 105.

Journal reference: J. Fungi 2018, 4, 105
DOI: 10.3390/jof4030105

Abstract

Candida glabrata has thoroughly adapted to successfully colonize human mucosal membranes and survive in vivo pressures prior to and during antifungal treatment. Out of all the medically relevant Candida species, C. glabrata has emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole + echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic to C. glabrata, since stable genetic resistance depends on mutation of drug target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription factor, PDR1, which controls expression of major drug transporters, such as CDR1 (azole resistance). However, another hallmark of C. glabrata is the ability to withstand drug pressure both in vitro and in vivo prior to stable ‘genetic escape’. Additionally, these resistance events can arise within individual patients, which underscores the importance of understanding how this fungus is adapting to its environment and to drug exposure in vivo. Here, we explore the evolution of echinocandin resistance as a multistep model that includes general cell stress, drug adaptation (tolerance), and genetic escape. The extensive genetic diversity reported in C. glabrata will be highlighted.

Subject Areas

Candida glabrata, drug resistance, tolerance, FKS, MSH2, echinocandin, azole

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