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Mitochondrial microdiversity of Candida albicans and its implications in hospital-acquired infections and patterns of mitochondrial genome macroevolution

Grant number: 13/07838-0
Support type:Regular Research Grants
Duration: September 01, 2013 - February 29, 2016
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Marcelo Ribeiro da Silva Briones
Grantee:Marcelo Ribeiro da Silva Briones
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo, SP, Brazil

Abstract

The goal of this proposal is to answer the question: How does Candida albicans mitochondria adapt or modulate the fungal adaptation to sudden growth condition shifts such as decreased oxygen concentration and increased temperature often associated with hospital-acquired infections? In other words, we aim to characterize the microadaptative response of Candida albicans mitochondria in low oxygen concentrations and increased temperatures and its relation to infectivity. In nosocomial infections, patients are often infected by yeasts present in abiotic surfaces such as catheters. Yeasts form biofilms on these surfaces where the oxygen tension is the same as the atmospheric level and the temperature is around 23oC. Upon shifting from the catheter into the patient's body these yeasts must adapt to lower oxygen tensions and 37oC. The effects of these changes in growth conditions have been studied separately in nonpathogenic yeasts of genus Saccharomyces, but have never been studied simultaneously in the pathogenic yeast C. albicans. In nonpathogenic yeasts, the adaptation to anaerobic growth involves the reduction in mitochondrial number and alterations in topology and sequence of mtDNA. We propose to use confocal microscopy to evaluate the morphology of cells and mitochondria, pulse field gel electrophoresis to observe alterations in mtDNA topology and comparative genome sequencing and analysis to study microdiversity patterns. We hypothesize that the synergistic response to increased temperature and decrease in the oxygen tension should cause changes in the morphology, distribution and the genome of mitochondria which may be related to phenotypic changes in the pathogen. Our results might have important implications for future studies on infectivity and epidemiology of Candida spp. because recent studies increasingly demonstrate the participation of mitochondria in the modulation of virulence and drug resistance in yeasts. Additionally, we plan to understand how these microevolutionary phenomena may explain, at least in part, the wide diversity of mitochondrial genome structures in the yeasts group. For this we propose we will compare the structure and synteny of C. albicans with mitochondrial of other Candida spp. through comparisons of complete mitochondrial genomes to verify if the regions rearranged during microevolution are homologous to regions involved in interspecific divergence. (AU)