Candida albicans is a human commensal yeast which colonizes the gastrointestinal tract at an early age can persist through life. In states of immunosuppression, C. albicans can escape from the gastrointestinal tract to invade mucosal surfaces or can spread through the bloodstream to invade various organs.
In this work, the gene for the APSES protein and EFG1 homolog EFH1 was shown to have increased expression in Candida albicans cells colonizing the gastrointestinal tract. Highlighting the importance of EFH1 regulation in the gastrointestinal tract, a strain deficient in efh1 was shown to have a hyperpersistence phenotype in the mouse gastrointestinal tract, while an EFH1 overexpressing strain was shown to have a colonization defect both in the gastrointestinal tract and in the oral cavity. This supports the model that EFH1 acts as a negative regulator of colonization, with C. albicans using expression of EFH1 to modulate colonization levels and prevent colonization from rising too high.
In vitro, microarray experiments showed that an EFH1 overexpressing strain displayed abnormal regulation of its carbon metabolism, simultaneously activating metabolic pathways associated with glycolysis and gluconeogenesis. Unlike the wild-type and efh1 null strains, the transcription profile of the EFH1 overexpressing strain in post-exponential phase had characteristics of both exponential and post-exponential phase growth.
During growth in the cecum, C. albicans was shown to have a transcription profile similar in many ways to that of exponential phase cells, yet also similar in many ways to that of post-exponential phase cells. In addition, despite growing primarily in yeast form, many hyphal genes were upregulated in the cecum. In studying the regulation of hyphal genes, one transcription factor, CPH2, was shown likely to play a role in the upregulation of hyphal genes, acting through another transcription factor, TEC1. Another putative target of CPH2 with a possible role in colonization was also demonstrated.
Examining the transcription profiles of efh1 null and EFH1 overexpressing strains in the cecum, both were seen to be highly similar to that of wild-type. A number of genes were found, however, which may be differentially regulated these strains. Differential regulation of these genes compared with wild-type may explain the difference in colonization phenotypes seen in the wild-type, efh1 null, and EFH1 overexpressing strains.