Publicação
Impact of alternative carbon sources on Candida pathogenesis
| Resumo: | Candida species are the most common cause of fungal infection in humans. Their capacity to cause infection is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. To assimilate alternative carbon sources and survive, they display a high degree of metabolic flexibility, which can influence their pathogenicity. Previous studies have shown that growth in alternative carbon sources influences the behaviour of these fungal pathogens, suggesting that some carboxylic acid transporters have a crucial role in biofilm formation and resistance to antifungal drugs. Furthermore, Candida species are able to grow outside the human body and colonize abiotic surfaces, being among the most prevalent causes of fungal infections on medical devices. Using in vitro C. glabrata biofilms, developed inside serum-coated triple-lumen catheters placed in 24-well plates, we assessed the effect of alternative carbon sources, namely acetic and lactic acids, in biofilm formation on central venous catheters. The role of these monocarboxylic acids transporters in this process, was also analysed. Our results demonstrate that the presence or absence of glucose, the acid concentration, as well the extracellular pH, influence biofilm formation. We also found that single mutations in monocarboxylic acid transporter genes identified in C. glabrata, (ADY2a, ADY2b, FPS1 and FPS2) did not impair biofilm formation. In glucose-poor niches, Candida albicans expresses JEN1 and JEN2 genes, encoding carboxylate permeases, which are important in the early stages of infection. In some of these environments, this fungus also faces different pH milieus, and the ability to adapt to them is essential for its pathogenicity. Our results showed Jen1p and Jen2p undergo endocytosis in response to prolonged growth on carboxylic acid containing medium, namely lactic and malic acid, being this a pH-dependent effect. These results also support the idea that Jen1p and Jen2p have specific affinity for different types of carboxylic acids. Globally, our results support the view that the adaptation of Candida cells to the alternative carbon source present in the host environment influences their pathogenicity. |
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| Autores principais: | Gonçalves, Alexandra do Carmo Gomes |
| Assunto: | Ciências Naturais::Outras Ciências Naturais |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Candida species are the most common cause of fungal infection in humans. Their capacity to cause infection is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. To assimilate alternative carbon sources and survive, they display a high degree of metabolic flexibility, which can influence their pathogenicity. Previous studies have shown that growth in alternative carbon sources influences the behaviour of these fungal pathogens, suggesting that some carboxylic acid transporters have a crucial role in biofilm formation and resistance to antifungal drugs. Furthermore, Candida species are able to grow outside the human body and colonize abiotic surfaces, being among the most prevalent causes of fungal infections on medical devices. Using in vitro C. glabrata biofilms, developed inside serum-coated triple-lumen catheters placed in 24-well plates, we assessed the effect of alternative carbon sources, namely acetic and lactic acids, in biofilm formation on central venous catheters. The role of these monocarboxylic acids transporters in this process, was also analysed. Our results demonstrate that the presence or absence of glucose, the acid concentration, as well the extracellular pH, influence biofilm formation. We also found that single mutations in monocarboxylic acid transporter genes identified in C. glabrata, (ADY2a, ADY2b, FPS1 and FPS2) did not impair biofilm formation. In glucose-poor niches, Candida albicans expresses JEN1 and JEN2 genes, encoding carboxylate permeases, which are important in the early stages of infection. In some of these environments, this fungus also faces different pH milieus, and the ability to adapt to them is essential for its pathogenicity. Our results showed Jen1p and Jen2p undergo endocytosis in response to prolonged growth on carboxylic acid containing medium, namely lactic and malic acid, being this a pH-dependent effect. These results also support the idea that Jen1p and Jen2p have specific affinity for different types of carboxylic acids. Globally, our results support the view that the adaptation of Candida cells to the alternative carbon source present in the host environment influences their pathogenicity. |
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