Partial Decay of Thiamine Signal Transduction Pathway Alters Growth Properties of Candida glabrata

• Published in: PloS one 2016-03, Vol.11 (3), p.e0152042-e0152042
• Main Authors: Iosue, Christine L, Attanasio, Nicholas, Shaik, Noor F, Neal, Erin M, Leone, Sarah G, Cali, Brian J, Peel, Michael T, Grannas, Amanda M, Wykoff, Dennis D
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Bacterial growth; Baking yeast; Biology; Biology and Life Sciences; Biosynthesis; Candida; Candida albicans; Candida glabrata; Candida glabrata - genetics; Candida glabrata - metabolism; Carbohydrates; Cellular signal transduction; Chromatography, High Pressure Liquid; Coculture Techniques; Computational Biology; Decay; Deoxyribonucleic acid; DNA; Drug Resistance, Fungal; Enzymes; Fungal Proteins - metabolism; Gene Deletion; Gene expression; Gene Expression Regulation, Fungal; Gene regulation; Genes; Genetic aspects; Genetic engineering; Genetic regulation; Genomes; Genomics; Growth; High-performance liquid chromatography; Kinases; Liquid chromatography; Metabolism; Microorganisms; Mutation; Opportunist infection; Phosphate esters; Phosphorylation; Physical Sciences; Plants (botany); Properties; Research and Analysis Methods; Saccharomyces; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Species; Species Specificity; Thiamine; Thiamine - metabolism; Thiamine Pyrophosphate - metabolism; Transcription (Genetics); Transcription, Genetic; Transduction; Vitamin B; Vitamin B1; Vitamin B6; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152042

The phosphorylated form of thiamine (Vitamin B1), thiamine pyrophosphate (TPP) is essential for the metabolism of amino acids and carbohydrates in all organisms. Plants and microorganisms, such as yeast, synthesize thiamine de novo whereas animals do not. The thiamine signal transduction (THI) pathway in Saccharomyces cerevisiae is well characterized. The ~10 genes required for thiamine biosynthesis and uptake are transcriptionally upregulated during thiamine starvation by THI2, THI3, and PDC2. Candida glabrata, a human commensal and opportunistic pathogen, is closely related to S. cerevisiae but is missing half of the biosynthetic pathway, which limits its ability to make thiamine. We investigated the changes to the THI pathway in C. glabrata, confirming orthologous functions. We found that C. glabrata is unable to synthesize the pyrimidine subunit of thiamine as well as the thiamine precursor vitamin B6. In addition, THI2 (the gene encoding a transcription factor) is not present in C. glabrata, indicating a difference in the transcriptional regulation of the pathway. Although the pathway is upregulated by thiamine starvation in both species, C. glabrata appears to upregulate genes involved in thiamine uptake to a greater extent than S. cerevisiae. However, the altered regulation of the THI pathway does not alter the concentration of thiamine and its vitamers in the two species as measured by HPLC. Finally, we demonstrate potential consequences to having a partial decay of the THI biosynthetic and regulatory pathway. When the two species are co-cultured, the presence of thiamine allows C. glabrata to rapidly outcompete S. cerevisiae, while absence of thiamine allows S. cerevisiae to outcompete C. glabrata. This simplification of the THI pathway in C. glabrata suggests its environment provides thiamine and/or its precursors to cells, whereas S. cerevisiae is not as reliant on environmental sources of thiamine.