In vivo and ex vivo comparative transcriptional profiling of invasive and non‐invasive Candida albicans isolates identifies genes associated with tissue invasion

Abstract

SummaryThe human pathogenic fungus Candida albicans can cause a wide range of infections and invade multiple organs. To identify C. albicans genes that are expressed during invasion of the liver, we used genome-wide transcriptional profiling in vivo and ex vivo. By analysing the different phases of intraperitoneal infection from attachment to tissue penetration in a time-course experiment and by comparing the profiles of an invasive with those of a non-invasive strain, we identified genes and transcriptional pattern which are associated with the invasion process. This includes genes involved in metabolism, stress, and nutrient uptake, as well as transcriptional programmes regulating morphology and environmental sensing. One of the genes identified as associated with liver invasion was DFG16, a gene crucial for pH-dependent hyphal formation, correct pH sensing, invasion at physiological pH and systemic infection.

Niche-specific gene expression during C. albicans infection

“…Consistent with the microarray data described above, e.g. [9,10], the SAP5 gene is expressed in multiple sites [28,29]. In contrast, SAP2 upregulation is seen in cells infecting the kidney [4,29] but not in cells infecting the esophagus or vagina [4,28,29].…”

“…A well studied example is upregulation of the gene encoding isocitrate lyase, an enzyme of the glyoxylate cycle, which was first demonstrated by Lorenz and Fink [13] and subsequently observed in numerous other studies [6,9,10,14,15]. These results show that in many host niches, metabolic adaptation for growth with low levels of glucose occurs.…”

“…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.…”

“…In their seminal work, Hube and coworkers performed microarray analysis of gene expression in C. albicans cells invading the mouse liver following intraperitoneal inoculation [9], C. albicans cells recovered from human oral thrush lesions [10] and C. albicans cells invading artificial reconstituted human epithelium (RHE) [10]. These studies allowed a comprehensive analysis of gene expression during infection.…”

Dectin-1 embraces Candida glabrata

“…This fact is quite relevant as diverse isolates of the same fungal species can trigger tremendously different responses. 3 The relevance of CLRs in antifungal immunity and in particular of Dectin-1, is well established in the field, especially based on the increased susceptibility of humans bearing mutations in this receptor or components of its signaling pathway. 4 However, in vivo data have been sometimes controversial; Dectin-1 was considered as required 5 and dispensable 6 for host defense against Candida albicans, while 2 works claimed that Dectin-1-deficient mice were susceptible 7 or resistant 8 to DSS-induced colitis.…”