The microenvironmental conditions during commensal colonization of the host may also play a role in the induction of the IgG response to certain cell surface proteins. Previous studies have evaluated characteristics common to the GI and/or vulvovaginal tract such as blood, hypoxia, iron restriction and weak acid as modifiers of gene expression [9, [51] [52] [53] . Intriguingly, the expressions of these genes share common features to the identified serodominant antibodies. Interestingly, genes transcriptionally upregulated in blood (Als1, Als3, Hwp1, Ece1, Hyr1, and Bgl2) were serodominant and cross-reactive with both positive and negative candidiasis individuals, as were genes up-regulated under hypoxic conditions (Als1, Als3, Hwp1, Rbt5, Utr2, and Tos1), iron restriction (Int1, Rbt5, and Fet35), and weak acid (Crp1, Fet35, and Ipf9655) ( Table 1) . Furthermore, some of the serodominant antigens (i.e. Als3, Ece1, Hwp1, and Rbt5) have been shown to be induced during the invasion of epithelial or endothelial cells [11, 33] . Therefore, the expression of the serodominant antigens in healthy individuals indicates the existence of permanent hostpathogen interplay during commensal colonization. In addition, the presence of serodominant IgGs in all 50 healthy individuals suggests that commensal colonization is much more prevalent than previously reported. One of the most challenging tasks in characterizing serodiagnostic antigens from C. albicans is the identification of discriminating peptides that can differentiate between commensal colonization and candidemia with high sensitivity and specificity. By profiling antibody response from patients with varying stages of candidemia against healthy individuals and candidemia-negative hospital patients, we have identified 13 diagnostic antigens for acute phase of candidemia and 33 for the early/mid convalescent candidemia. The serologic signature in candidemia patients likely reflects an alteration in the level of those proteins due to a change either in transcription and/or protein stability. Stage-and tissuespecific gene expression during the course of systemic infection is expected as C. albicans cells transition through differing microenvironments of the host. Among the 13 diagnostic antigens for acute candidemia, three are associated with drug resistance (Cdr1, Cdr4, and Yor1) [36] . The exposure to antifungal drugs in patients undergoing acute candidemia may have acted as an additional environmental stress that stimulates the expression of these antifungal drug transporters [54] . Intriguingly, two out of the 13 biomarkers are the osmosensors Sln1 and Nik1 for the HOG pathway that is responsible for osmotic and oxidative stress adaptation in C. albicans [34, 35] . The host-pathogen interaction commonly associated with oxidative stress is typically seen during phagocytosis by neutrophils, the initiating immune response to C. albicans overgrowth and infection. Furthermore, a study of global transcriptional responses to oxidative stress observed an increase in the transcriptional expression of CDR4 (4.1-fold), RAS2 (2.5-fold) and ALS9 (1.5-fold) [35] . Taken together, our data indicates a strong correlation between the IgG response to oxidative stressrelated cell surface proteins and the initial cell-mediated immune response during acute candidemia. In further agreement, previous studies have shown that oxidative stress functions are primarily induced when C. albicans is initially exposed to human blood or following phagocytosis by neutrophils and granulocytes [7, 9, 10, 55] . The 33 convalescent diagnostic antigens include proteins involved in iron acquisition, cell wall biogenesis, membrane lipid organization, and drug resistance. Of particular interest is the dramatic increase in antibodies to proteins for iron acquisition (Cfl91, ferric reductase; Rbt5 and Csa1, hemoglobin receptors; and Flc1, heme uptake). Iron is an essential nutrient for C. albicans. Circulating iron in serum is bound to transferrin and ferric reductases are required in the acquisition of iron from transferrin. Interestingly, Cfl91 is found as a biomarker for both acute and convalescent candidemia patients. Of particular interest is the increase antibody response to hemoglobin and heme-related proteins as these molecules are normally sequestered in erythrocytes [56] . The proteins Rbt5, Csa1 and Flc1 are required for iron acquisition from hemoglobin or heme [39, 40] and are diagnostic antigens only for convalescent candidemia. Thus, it is interesting to speculate whether free hemoglobin becomes a by-product of lysed erythrocytes after post-operative surgery or other invasive clinical procedures. Nevertheless, the data from this study should provide critical information for the development of diagnostic antigenic profiles for patients at risk for candidemia and for the assessment of progression of hematogenously disseminated candidiasis. Future studies will need to be done to determine whether serological differences exist between superficial and systemic infections, as well as commensal sensitization. The development of the antigenic profiles over the course of candidiasis (acute infection, early convalescence, and mid convalescence) may also provide insight into a protective humoral response against C. albicans. Even though previous sensitization to commensal colonization does not limit mortality or even morbidity in patients, experimental studies have identified protective antibodies against hematogenously disseminated candidiasis, such as heat shock protein 90 (Hsp90) or b-mannan [57] [58] [59] [60] . Future studies will need to address whether the serodiagnostic antigens identified in this study could provide protection from hematogenously disseminated candidiasis. Of particular interest are the convalescent serodiagnostic antigens where the EC antigen intensity is significantly greater than the AI antigen intensity, which may possibly indicate the selection of a protective antibody response.