The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival
| Autor: | Veridiana Tofik, Marcelo A. Vallim, Kevin Felipe Martho, João Daniel Santos Fernandes, Renata C. Pascon |
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| Rok vydání: | 2015 |
| Předmět: |
Amino Acid Transport Systems
Transcription Genetic Nitrogen Genes Fungal lcsh:Medicine Microbial Sensitivity Tests Saccharomyces cerevisiae Microbiology Fungal Proteins Gene Expression Regulation Fungal lcsh:Science Amino acid synthesis chemistry.chemical_classification Cryptococcus neoformans Fungal protein Multidisciplinary Genes Essential Microbial Viability biology Permease Catabolism Gene Expression Profiling lcsh:R Tryptophan biology.organism_classification Amino acid Biosynthetic Pathways Complementation Phenotype chemistry Biochemistry Mutation lcsh:Q RNA Interference Gene Deletion Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 7, p e0132369 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR). We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8). The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i) quality of nitrogen (Nitrogen Catabolism Repression, NCR) and carbon sources (Carbon Catabolism Repression, CCR), (ii) amino acid availability in the extracellular environment (SPS-sensing) and (iii) nutritional deprivation (Global Amino Acid Control, GAAC). This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro. |
| Databáze: | OpenAIRE |
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