Candida albicans drug resistance – another way to cope with stress

Richard D Cannon,Masakazu Niimi,Kyoko Niimi,Koichi Tanabe,Brian C Monk,Erwin Lamping,Ann R Holmes

doi:10.1099/mic.0.2007/010405-0

Richard D Cannon, Masakazu Niimi + Show 5 more

Open Access

https://doi.org/10.1099/mic.0.2007/010405-0

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Abstract

There are relatively few classes of antifungal drugs. This restricts clinicians' therapeutic choices and these choices are further reduced by the emergence of drug resistance. Exposure to antifungal drugs represents an environmental stress for the fungal pathogen Candida albicans. The immediate response of C. albicans to antifungals may be drug tolerance, which can lead to drug resistance. This article examines C. albicans drug resistance from the perspective of it being a stress response and investigates how commonality with other stress-response pathways gives insights into the prospects for overcoming, or preventing, drug resistance.

Highlights

Antimicrobial drug resistance is an important biological phenomenon that has a considerable impact on animal and human health
The cAMP-protein kinase A (PKA) signal transduction pathway is involved in C. albicans’ response to antifungal stress (Fig. 2); adenylate cyclase (CDC35) mutants no longer respond to azoles with upregulation of CDR1 (Jain et al, 2003)
The exposure of C. albicans to antifungal drugs will induce stress responses that are dependent on the dose and the nature of the drug

Summary

Introduction

Antimicrobial drug resistance is an important biological phenomenon that has a considerable impact on animal and human health. Polyenes are thought to cause oxidative damage (Sanglard & Bille, 2002) The azole antifungals, such as the triazole fluconazole, interfere with sterol biosynthesis (Fig. 1a). The cAMP-PKA (protein kinase A) signal transduction pathway is involved in C. albicans’ response to antifungal stress (Fig. 2); adenylate cyclase (CDC35) mutants no longer respond to azoles with upregulation of CDR1 (Jain et al, 2003). The serine/threonine protein phosphatase calcineurin is highly conserved in eukaryotes and is activated in response to several stresses It has important physiological roles in C. albicans, and is essential for survival during membrane stress (Cruz et al, 2002). Calcineurin plays an important role in the http://mic.sgmjournals.org

Drug resistance is a Candida albicans stress response

Antifungal drug resistance is a stress response

Antifungal drug tolerance

Prospects of overcoming drug resistance

Findings

Conclusions