05) in the list of genes differentially expressed between day 8 and day 2 spherules. The most significant enriched GO term was “sulfur compound

metabolic process” (corrected p-value = 0.046). Sixteen genes were downregulated in this data set and one was upregulated. We see downregulation of 5′-methylthioadenosine phosphorylase (CIMG_01361, -7.45 fold), phosphoadenosine phosphosulfate reductase (CIMG_00456, -4.65 fold), two genes coding for adenylyl-sulfate kinase Silmitasertib cost (CIMG_00454, -4.22 fold and CIMG_06918, -2.65 fold) and sulfite reductase (CIMG_00269, -2.94 fold) in day 8 spherules. Two of these genes were upregulated in day 2 spherules compared to mycelia. All these genes are involved in accumulating sulfide. This suggests that C. immitis spherules have no difficulty accumulating enough sulfur for their needs as A-769662 mouse they mature. Upregulated or downregulated genes in day 2, day 4 and day 8 spherules We identified 153 genes that were upregulated more than two fold in day 2 spherules, day 8 spherules and day 4 spherules in the Whiston study [13]. 140 genes were downregulated more than two fold in all

three spherule samples. 57% of the upregulated genes and 42% of the downregulated genes had no function annotation (Additional file 7: Table S4). Many of these unannotated genes were highly differentially expressed suggesting that they may be important for spherule development. One upregulated gene that has not been discussed is opsin-1 (CIMG_08103, maximal upregulation 25.72). This gene is closely related to the bacterial rhodopsin gene coding for G protein coupled

receptors; its function in fungi has not been determined [59]. Another gene that was upregulated Bupivacaine at all three spherule time points was the sulfite transporter Ssu1 (CIMG_05899, maximum upregulation 6.37). Downregulated genes of interest include several glucosidases, glucanases and a chitosanase. Two septin genes are downregulated in spherules. Septin genes are important regulators of the cytoskeleton and play a role in determining cell shape [60]. Why these genes are downregulated is unclear since the spherule is undergoing extensive cellular remodeling. Perhaps septins are required for polar growth and other regulators are needed for isotropic spherule growth. Further analysis of the relatively small group of genes that are consistently up- or downregulated throughout spherule development may be useful for understanding the pathogenic phase of this organism. Comparison of results to those obtained in other pathogenic fungi The dimorphic pathogenic fungi are phylogenetically closely related [61] so it is reasonable to ask if genes important for conidium to yeast transformation in those pathogens are also important for arthroconidia to spherule transformation in Coccidioides. One H. capsulatum gene that is required for mycelium to yeast transformation is the alpha amylase (AMY1) gene.