Phenotypic analysis of Aspergillus fumigatus exposed to different concentrations of carbonic anhydrase inhibitors

• Grant number: 12/03762-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2012
• Effective date (End): June 30, 2013
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Márcia Eliana da Silva Ferreira
• Grantee: Mariane Massufero Vergilio
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Aspergillus fumigatus is a saprophytic and filamentous fungus of great importance in the environment for recycle carbon and nitrogen. This fungus can be found in all regions of the world. However, in the last two decades, with the spread of AIDS, as well as the development of new immunosuppressive drugs and techniques for organ transplants, this ascomycete is no longer just a saprophytic fungus of minor importance and has become one of the major human pathogens. Invasive fungal diseases are serious public health problem and cause deaths worldwide. During the infection process, the fungus A. fumigatus faces a dramatic variation in the carbon dioxide (CO2) concentrations. In its natural habitat, CO2 represents only 0.033% of atmospheric gases, while in the infected host, the concentration can arrive up to 6% in the bloodstream and in tissues where breathing occurs. The carbonic anhydrase, an enzyme that facilitates the interconversion between CO2 and HCO3- in the body, has been studied as an important factor in the virulence and differentiation of some pathogenic fungi. The search for carbonic anhydrase inhibitors is therefore of great importance, because these molecules are applicable in the generation of new therapeutic agents and / or new experimental tools for basic and applied research. Thus, this study aims to determine if A. fumigatus has sensitivity against some carbonic anhydrase inhibitors. For this, different inhibitors concentrations will be carried through assays using inhibitors that possess greater selectivity for the beta class of the carbonic anhydrases (sodium Format, acid 4-metoxibenzóico and acid 4-hidroxibenzóico), carbonic anhydrase class that belong the four anidrases of the A. fumigatus fungus. (AU)