Differential activation of a Candida albicans virulence gene family during infection

Abstract

The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections in immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, which involves the activation of appropriate sets of genes in response to complex environmental signals. We have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated in C. albicans virulence, at various stages of the infection process. Our results demonstrate that SAP expression depends on the type of infection, with different SAP isogenes being activated during systemic disease as compared with mucosal infection. In addition, the activation of individual SAP genes depends on the progress of the infection, some members of the gene family being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, the number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technology allows the elucidation of gene expression patterns at different stages of the fungus-host interaction, thereby revealing regulatory adaptation mechanisms that make C. albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which certain virulence genes may play a role.

Differential gene expression in the pathogenic dermatophyte Arthroderma benhamiae in vitro versus during infection

“…These findings support the idea that multiple members of protease gene families in dermatophytes are not redundant but fulfil specific roles during infection, and may not be dedicated exclusively to protein degradation and nutrient supply. Likewise, the evolution and differential expression of a virulence gene family encoding secreted aspartic proteases in the human pathogenic yeast C. albicans has also been demonstrated to be linked to infection (reviewed by Naglik et al, 2003;Staib et al, 2000). Our results derived specifically from cutaneous infection of guinea pigs by A. benhamiae.…”

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.…”

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

“…It can also induce life‐threatening systemic infections known as candidemia in immunocompromised patients (Miller et al ., 2001; Pappas et al ., 2003). C. albicans has a distinguishing feature, the yeast‐to‐hyphae dimorphism, which is the most important virulence factor that enables C. albicans to infect humans (Madhani and Fink, 1998; Brown and Gow, 1999; Staib et al ., 2000). During the initial stage of infection, C. albicans cells exhibit a planktonic yeast morphology that is avirulent, and a subsequent transition from yeast to hyphae leads to tissue invasion in patients (Sudbery et al ., 2004; Saville et al ., 2003; Lo et al ., 1997; Finkel and Mitchell, 2011).…”