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The phosphorylated form of thiamine (Vitamin B 1 ), 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 B 6 . 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.

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