Abstract
Hsp12p is considered to be a small heat shock protein and conserved among fungal species. To investigate the expression of this heat shock protein in the fungal pathogen Candida albicans we developed an anti-CaHsp12p antibody. We show that this protein is induced during stationary phase growth and under stress conditions including heat shock, osmotic, oxidative and heavy metal stress. Furthermore, we find that CaHsp12p expression is influenced by the quorum sensing molecule farnesol, the change of CO2 concentration and pH. Notably we show that the key transcription factor Efg1p acts as a positive regulator of CaHsp12p in response to heat shock and oxidative stress and demonstrate that CaHsp12p expression is additionally modulated by Hog1p and the cAMP-PKA signaling pathway. To study the function of Hsp12p in C. albicans we generated a null mutant, in which all four CaHSP12 genes have been deleted. Phenotypic analysis of the strain shows that CaHSP12 is not essential for stress resistance, morphogenesis or virulence when tested in a Drosophila model of infection. However, when overexpressed, CaHSP12 significantly enhanced cell-cell adhesion, germ tube formation and susceptibility to azole antifungal agents whilst desensitizing C. albicans to the quorum sensing molecule farnesol.
Highlights
Candida albicans is an ascomycete yeast which can be found in the gastrointestinal tract and the oral or vaginal mucosa of many otherwise healthy individuals [1]
Database sequences show that there are two HSP12 genes present in the genome of Candida dublinensis, which is closely related to C. albicans, but only one in S. cerevisiae, C. glabrata, Candida tropicalis, Candida guiliermondii, Candida lusitaniae and Cryptococcus neoformans
To determine if both copies of C. albicans HSP12 (CaHSP12) are expressed, qRT-PCR was carried out in a strain in which one copy of CaHSP12 had been deleted (HSP12KO2). This showed a reduction of CaHSP12 expression by 50% compared to the parent strain (Figure 1B) suggesting that both copies are expressed in C. albicans
Summary
Candida albicans is an ascomycete yeast which can be found in the gastrointestinal tract and the oral or vaginal mucosa of many otherwise healthy individuals [1]. It is a major opportunistic fungal pathogen, causing superficial infections of mucosa and skin, or life-threatening invasive infections when either the innate or acquired immune system is compromised [1,2]. The ability to undergo a reversible morphological transition in response to environmental changes is an additional advantage of C. albicans host adaptation Both stress response and polymorphism are considered major virulence factors of C. albicans [8,9]. Previous studies have shown that the Hog1p MAPK signaling pathway plays an important role in regulation of stress response [8] whereas C. albicans polymorphism is controlled by multiple signaling pathways including the Efg1p-mediated cAMP pathway, Cph1pmediated MAPK, Rim101p and Tup1p dependant pathways [6,10,11,12]
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