Resistance in Candida albicans: Exploring the Cell Wall Barrier by Proteomics

Bruno Maras Giuseppina,Mignogna Letizia Angiolella

doi:10.4172/2167-7700.1000165

Bruno Maras Giuseppina, Mignogna Letizia Angiolella

Open Access

https://doi.org/10.4172/2167-7700.1000165

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Journal: Chemotherapy	Publication Date: Jan 1, 2015
License type: cc-by

Affiliation: Sapienza University of Rome

Abstract

The incidence of candidiasis has dramatically increased and bloodstream infections due to different species of Candida are becoming a prime cause of morbidity and mortality in different types of immunocompromised patients. Azole and echinocandin drug resistance accounts for the dramatic increase in incidence of nosocomial bloodstream candidiasis found in recent years. Cell wall constitutes the barrier between the yeast and the host and resistant strains change the proteome of this compartment. In the last decade different proteomic platforms have been applied to study cell wall and markers of resistance to drugs have been pointed out. Modulation of these proteins seem to suggest that although resistance is based on a specific mutation able to counteract the toxicity of the antifungal drug, a set of other molecular modifications takes place contemporary or subsequently the establishment of the resistance and seems to support the viability of the resistant yeast. Profiled proteins by proteomics may be valuable in design therapy using classical antifungal along with complementary drugs able to abolish pathways that strengthen the resistance and attenuate virulence of the mutated cell.

Highlights

Candida albicans, adimorphic opportunistic human pathogen yeast, is the most prominent cause of oro-pharyngeal, vaginal and invasive candidiasis in man [1]
Oro-pharyngeal infections are very common in human immunodeficiency virus (HIV)-infected individuals and patients with acquired immune deficiency syndrome (AIDS), while deep-seated infections are frequent in neutropenic patients under chemotherapy [2,3]
The echinocandin target, ß-1,3-D-glucan synthase, is a fungal-specific multi-subunit enzyme complex comprised of Rho, a GTP-binding protein, which helps regulate the overall activity of glucan synthase and a catalytic subunit Fks encoded by three related genes, FKS1, FKS2, and FKS3 [6]

Summary

Introduction

Adimorphic opportunistic human pathogen yeast, is the most prominent cause of oro-pharyngeal, vaginal and invasive candidiasis in man [1]. Available therapies reside on antifungal drugs belonging to azole and echinocandin families that interfere with different aspects of fungal metabolism. In Candida, azole antifungals target protein Erg11p involved in the biosynthesis of ergosterol, the main sterol of the membranes of the fungal cell. This protein is located at the inner face of the membrane of the smooth endoplasmic reticulum, engaged in the synthesis of lipids, including oils, phospholipids and steroids. The echinocandin target, ß-1,3-D-glucan synthase, is a fungal-specific multi-subunit enzyme complex comprised of Rho, a GTP-binding protein, which helps regulate the overall activity of glucan synthase and a catalytic subunit Fks encoded by three related genes, FKS1, FKS2, and FKS3 [6]

Candida resistance to antifungal drugs

Molecular studies of Candida cell wall

Conclusion