Full text
| |
| Author(s): |
Fernando Ruy
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2007-02-03 |
| Examining board members: |
Alicia Juliana Kowaltowski;
Iolanda Midea Cuccovia;
Claudia Barbosa Ladeira de Campos;
Fernanda Ramos Gadelha;
Rosana Almada Bassani
|
| Advisor: | Alicia Juliana Kowaltowski |
| Abstract | |
Candida albicans is an important pathogen in humans. A crucial feature of this microorganism is its ability to survive in different environments within the host with distinct oxygen tensions. It is believed that this flexibility is due the expression of alternative oxygen reduction pathways and the control of electron flux between them and the classical respiratory chain. The presence of these pathways may also be related to the high resistance these fungi present to drugs, since the inhibition of one electron transport pathway can be compensated by the activity of the others. In this study we confirm the presence of three electron transport pathways in Candida albicans: the classical respiratory chain (CRC), a parallel chain (PAR) and an alternative oxidase (AOX). We also evaluated the contribution of each pathway toward yeast growth. To do so, we measured cellular proliferation in the absence and presence of electron transport inhibitors. Antimycin A and KCN, which inhibit Complexes III and IV, respectively, totally prevented cellular growth. BHAM, an AOX inhibitor, also promoted inhibition of yeast growth. Surprisingly, the presence of rotenone, an inhibitor of respiratory Complex I, inhibited yeast growth only partially. These results were then correlated with oxygen uptake in mitochondrial and cell suspensions, which revealed that rotenone and BHAM promote only partial respiratory inhibitions. Concentrations of antimycin and KCN which promoted partial respiratory inhibition had distinct effects on growth. While antimycin totally prevented cell proliferation, KCN did not. We also evaluated the levels of reactive species of oxygen (ROS) and oxidized glutathione in the cells incubated in the presence of respiratory inhibitors. The levels of ROS in antimycin-treated cells were significantly higher than in the other groups. Finally, we observed an increase of oxidized glutathione in cells incubated in the presence of antimycin and BHAM. These experimental findings suggest that inhibitions of complex III of the CRC and AOX prevent Candida albicans growth by promoting oxidative stress, indicating the importance of these pathways to ensure yeast viability (AU) | |