Evidence for Differential Expression ofCandida albicansVirulence Genes during Oral Infection in Intact and Human Immunodeficiency Virus Type 1–Transgenic Mice

Abstract

To comprehensively assess the in vivo expression of Candida albicans hydrolytic enzyme genes during oropharyngeal candidiasis (OPC), a controlled sequential analysis of the temporal expression of individual members of the SAP (secretory aspartyl proteinase) gene family and PLB1 (phospholipase B) in a murine model of OPC was conducted. Acute infections in intact C3H and DBA/2 mice were terminated by clearance of C. albicans within 7 days after oral inoculation, but transgenic (Tg) mice expressing human immunodeficiency virus type 1 were persistently colonized until a final outgrowth before death. In contrast to the sustained expression of other SAP genes and PLB1, SAP7 and SAP8 were conspicuously distinguished by their transient expression in both intact and Tg mice. SAP5 and SAP9 were most strongly expressed throughout the course of infection in the Tg mice. These findings indicate that expression of individual members of the C. albicans SAP gene family is differentially regulated during experimental OPC.

Phylogeny and evolution of the aspartyl protease family from clinically relevant Candida species

“…albicans SAP1-3 and SAP4-6 gene families are not pseudogenes that have subsisted to purifying selection and concerted evolution, but apparently have acquired new and specific functions in nitrogen metabolism, switching, and cell adherence (Cassone et al 2002, Felk et al 2002, Ripeau et al 2002, Schofield et al 2003. C. tropicalis has only one gene (SAPT4) related to the C. albicans SAP1-3 and SAP4-6 families.…”

Niche-specific gene expression during C. albicans infection

“…These genes, and others, are highly expressed in laboratory-grown hyphae [19,[23][24][25]. In many infection studies, C. albicans cells are predominantly in the hyphal form [9,13,26], and expression of the hypha-coregulated genes is seen in these situation [9][10][11]13,[26][27][28][29][30][31]. Unexpectedly, expression of these genes is also seen in yeast cells during commensal colonization of the murine intestinal tract by C. albicans [32], showing that in the host, expression of these genes is not strictly tied to cellular morphology.…”

Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis

“…Immunohistological analysis of biopsies from patients with oral candidiasis have been performed [5][6][7] but such studies are not amenable to experimental manipulation and so can only provide limited information. Murine models of oral candidiasis have identified several potential virulence factors that may play a role in pathogenesis [8][9][10], but since C. albicans does not naturally colonise the murine oral cavity [11] it is not clear how representative these studies are. Moreover, there are significant differences between the innate immune systems of humans and mice [12] which may make the results of murine studies difficult to interpret.…”