Evaluation of gene expression of Trichophyton rubrum co-culture of keratinocytes in response to infection and exposure of antifungal

• Grant number: 13/15907-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2013
• Effective date (End): January 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Ana Lucia Fachin Saltoratto
• Grantee: Ádrian Colantonio de Oliveira
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil

Abstract

The dermatophyte Trichophyton rubrum (T.rubrum) is the most frequent cause of superficial dermatomycoses in Brazil and worldwide. Dermatophytes are adapted to grow in nail, skin and hair by use of a variety of host proteins (especially keratin) as a nutrient. To understand the complex interactions with the host fungus can identify genes expressed simulating the infection of human skin by using human cultured keratinocytes. Moreover, despite the importance of mycoses, only a limited number of antifungal drugs are currently available on the market due to the lack of appropriate targets, as well as some are very toxic to humans. Recent evidence suggests that the enzyme fatty acid synthase (FAS) that catabolizes the synthesis of fatty acid, has great potential as a new antifungal target. Natural inhibitors of FAS different chemical structures have been isolated in many medicinal plants. Chalcones are flavonoids produced by plants and present several interesting biological activities, especially antimicrobial and antifungal. One of the mechanisms of action of most of chalcones is the inhibition of cell wall biosynthesis, but there is evidence in the literature that it can also act in the activity of the enzyme fatty acid synthase (FAS). Antifungal agents exert their activity through a variety of molecular mechanisms that are most often poorly understood in infections caused by dermatophytes. Terbinafine, as most conventional antifungal drugs acts on the plasma membrane of the fungus, interfering with, in most cases, metabolism of ergosterol. Thus, this aims is the evaluation of gene expression of the Trichophyton rubrum growth in co-cultured keratinocytes in response to fungal infection and exposure of antifungals. (AU)