Changes in the Proteome of Candida albicans in Response to Azole, Polyene, and Echinocandin Antifungal Agents

Abstract

The yeast Candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectroscopy following exposure to representatives of the azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We identified 39 proteins whose abundance changed in response to ketoconazole exposure. Some of these proteins are involved in ergosterol biosynthesis and are associated with azole resistance. Exposure to amphotericin B altered the abundance of 43 proteins, including those associated with oxidative stress and osmotic tolerance. We identified 50 proteins whose abundance changed after exposure to caspofungin, including enzymes involved in cell wall biosynthesis and integrity, as well as the regulator of ␤-1,3-glucan synthase activity, Rho1p. Exposure to caspofungin also increased the abundance of the proteins involved in oxidative and osmotic stress. The common adaptive responses shared by all three antifungal agents included proteins involved in carbohydrate metabolism. Some of these antifungal-responsive proteins may represent potential targets for the development of novel therapeutics that could enhance the antifungal activities of these drugs.

Cambios morfológicos e inhibición del crecimiento de Candida albicans en presencia de una solución de sulfato de zinc

“…Adicionalmente, la candidiasis oral y orofaríngea (7,8), son las infecciones fúngicas más comunes en pacientes oncológicos sometidos a tratamiento antineoplásico; paciente con grandes estadías hospitalaria (9), también se encuentra presente en algunos estados fisiológicos como enfermedades metabóli-cas, endocrinopatías, síndrome de inmunodeficiencia adquirida, uso de medicamentos, intervenciones quirúrgicas, en donde se pueden presentar posibles fallas en los tratamientos instaurados con antimicó-ticos, adquiriendo resistencia (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Actualmente se ha visto este hongo, también implicado en procesos de resistencia a sustancias anti fúngicas ya existentes (10)(11)(12), razón por la que se considera de gran importancia la investigación en productos que inhiban el crecimiento de este microorganismo.…”

Echinocandins Versus Dated Antifungals in Combination Against Opportunistic Mycotic Infections

“…Lately, the major fluctuations have been observed in a protein [AFUA_1G12250] in mitochondria, whose intensity reduced more than 16 times in the secreted portion. Earlier studies revealed the probable importance of this protein as a biomarker exclusively to CAS as it was not reported while A. fumigatus was exposed to either voriconazole or AmpB [61][62].…”

“…Some enzymes catalyzing cell wall biosynthesis and the regulating BG synthase were also acknowledged [62].…”

Combining Proteomic Strategies and Molecular Display Technology for Development of Vaccines against Candida albicans

“…Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) has been widely used for proteomic investigations of C. albicans [11,12]. 2D-PAGE has typically been used for protein separation for proteome analysis.…”