Candida albicans Sun41p, a Putative Glycosidase, Is Involved in Morphogenesis, Cell Wall Biogenesis, and Biofilm Formation

Fraunhofer Institute for Interfacial Engineering and Biotechnology, Nobelstrasse 12, 70569 Stuttgart, Germany.
Eukaryotic Cell (Impact Factor: 3.18). 12/2007; 6(11):2056-65. DOI: 10.1128/EC.00285-07
Source: PubMed


The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this
family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis.
In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in
the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable
to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of
cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved
in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the
host-pathogen interaction.

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    • "One can speculate that SUN proteins may participate in remodeling the cell wall during the exponential-to-diauxic/stationary phase transition and in stationary cells they could affect cell wall structures from the “outside”. SUN proteins may affect cell morphogenesis, as was described for C. albicans Sun41p, which is involved in hyphae formation [15], [16], [25] and possibly secreted [25]. A second possibility that cannot be excluded is that these proteins are removed from the cell wall after accomplishing their task during cell division and septation, and that their presence in the extracellular medium is just a consequence of this release. "
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    ABSTRACT: The SUN family is comprised of proteins that are conserved among various yeasts and fungi, but that are absent in mammals and plants. Although the function(s) of these proteins are mostly unknown, they have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the cells in different growth phases and their production is affected by the level of oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the growth phase of both yeast liquid cultures and colonies. Culture transition to slow-growing or stationary phases is linked with a decreased cellular concentration of Sim1p and Sun4p and with their efficient release from the cells. In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to compounds influencing cell wall composition and integrity (such as Calcofluor white and Congo red) differently when growing on fermentative versus respiratory carbon sources. In contrast, Uth1p is essential for cell resistance to boric acids irrespective of carbon source. In summary, our novel findings support the hypothesis that SUN family proteins are involved in the remodeling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions. The finding that Uth1p is involved in cell sensitivity to boric acid, i.e. to a compound that is commonly used as an important antifungal in mycoses, opens up new possibilities of investigating the mechanisms of boric acid's action.
    PLoS ONE 09/2013; 8(9):e73882. DOI:10.1371/journal.pone.0073882 · 3.23 Impact Factor
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    • "Under this condition HSP12OE settled quicker than the control (Figure 4C), demonstrating that cell aggregation was not secondary to filamentation. Cell adhesion of HSP12OE was also tested using the microtitre plate cell adhesion XTT reduction assay [48], [49]. This showed that HSP12OE adhesion to plastic is much stronger when compared to the control (Figure 4D). "
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    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 CO(2) 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.
    PLoS ONE 08/2012; 7(8):e42894. DOI:10.1371/journal.pone.0042894 · 3.23 Impact Factor
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    • "Interestingly, mass-spectrometry analysis of the secretome of SC5314 identified Sun41p as well as Sim1p/Sun42p as secreted proteins of cells growing as blastospores as well as those forming hyphae. This suggests that Sun41p is active at the outer rim of the cell wall (Hiller et al., 2007). In addition, in a parallel study Norice et al. (2007) could show that SUN41 indeed is required for virulence in a mouse model of systemic infection. "
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    ABSTRACT: Infectious diseases have long been regarded as losing their threat to mankind. However, in the recent decades infectious diseases have been regaining grounds and are back in the focus of research. This is also due to the fact that medical progress has enabled us to treat and cure a much higher fraction of severe diseases or trauma, resulting in a significant proportion of temporarily or constantly immune-suppressed patients. Infectious diseases result from the interplay between pathogenic microorganisms and the hosts they infect, especially their defense systems. Consequently, immune-suppressed patients are at high risk to succumb from opportunistic infections, like Candida infections. To study the balance between host and C. albicans with regard to the establishment of disease or asymptomatic, commensal colonisation, we developed host-pathogen interaction systems to study both the adaptation of C. albicans to different epithelia as well as to investigate the sensors of the innate immune system, the pattern recognition receptors. These host-pathogen interaction systems, as well as some of the results gained are described in this review.
    International journal of medical microbiology: IJMM 06/2011; 301(5):384-9. DOI:10.1016/j.ijmm.2011.04.004 · 3.61 Impact Factor
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