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

ABSTRACT 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.

Download full-text


Available from: Steffen Rupp, Aug 13, 2015
1 Follower
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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 · 3.42 Impact Factor
  • Source
    • "Transcript profiling has identified genes that show increased or decreased expression in biofilms relative to planktonic cells and it has been hypothesized that these genes might play some role in biofilm formation. For instance, C. albicans SUN41 was among the genes that showed high upregulation upon biofilm growth (Garcia- Sanchez et al., 2004) and was subsequently shown to be required for biofilm formation, possibly through its contribution to morphogenesis and/or matrix production (Firon et al., 2007; Hiller et al., 2007; Norice et al., 2007). Yet, other examples showed no strict correlation between differential regulation in biofilm versus planktonic growth and contribution to biofilm formation (Moreno-Ruiz et al., 2009; Sellam et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The fungal pathogen Candida albicans forms therapeutically challenging biofilms on biomedical implants. Using a transcript profiling approach genes whose expression is favoured upon biofilm growth compared with planktonic growth have been previously identified. Knock-out mutants for 38 of these genes were constructed, six of which showed a specific defect in biofilm formation. Among these genes, TYE7 that encodes a transcriptional activator of glycolytic genes in planktonic and biofilm growth conditions was identified as being required for the cohesiveness of biofilms. Biofilms formed by the tye7Δ knock-out mutant showed a hyperfilamentous morphology, and growth of this mutant on solid medium under hypoxia was also associated with the production of hyphae. Similar to TYE7 inactivation, inhibition of glycolysis or ATP synthesis using oxalate or an uncoupler, respectively, triggered morphogenesis when a wild-type strain was grown under hypoxia. These treatments also induced the formation of weakly cohesive, hyper-filamentous biofilms by a wild-type strain. Our data indicate that a hypoxic environment is generated within C. albicans biofilms and that continued biofilm development requires a Tye7p-dependent upregulation of glycolytic genes necessary to adapt to hypoxia and prevent uncontrolled hyphal formation. Thus, adaptation to hypoxia is an integral component of biofilm formation in C. albicans.
    Molecular Microbiology 03/2011; 80(4):995-1013. DOI:10.1111/j.1365-2958.2011.07626.x · 5.03 Impact Factor
  • Source
    • "Importantly, of the 44 secretory proteins we were able to identify in the growth medium, only Mp65, Sun41 and Tos1 seemed to be consistently and abundantly present under all four conditions. This observation is supported by previous studies (Hiller et al., 2007; Maddi et al., 2009). The corresponding genes are highly conserved in many fungi, underlining their functional importance. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenic fungus Candida albicans secretes a considerable number of hydrolases and other proteins. In-depth studies of the C. albicans secretome could thus provide new candidates for diagnostic markers and vaccine development. We compared various growth conditions differing in pH, temperature and the presence of the hyphal inducer N-acetylglucosamine. The polypeptide content of the growth media was ca. 0.1-0.2% of the total biomass. Using LC-tandem mass spectrometry, we identified 44 secretory proteins, the transmembrane protein Msb2, six secretory pathway-associated proteins and 28 predicted cytosolic proteins. Many secretory proteins are wall-related, suggesting that their presence in the growth medium is at least partially due to accidental release from the walls. Als3, Csa2, Rbt4, Sap4 and Sap6 were enriched in the medium of hyphal cultures; Bgl2, Cht3, Dag7, Eng1, Pir1, Rbe1, Scw11, Sim1/Sun42, Xog1 and Ywp1 in the medium of yeast cells; and Plb4.5 in pH 4 medium. Seven proteins (Cht3, Mp65, Orf19.5063/Coi1, Scw11, Sim1, Sun41 and Tos1) were consistently present under all conditions tested. These observations indicate that C. albicans tightly regulates its secretome. Mp65, Sun41, and Tos1 were each predicted to contain at least one highly immunogenic peptide. In total, we identified 29 highly immunogenic peptides originating from 18 proteins, including two members of the family of secreted aspartyl proteases. Fifty-six peptides were identified as proteotypic and will be useful for quantification purposes. In summary, the number of identified secretory proteins in the growth medium has been substantially extended, and growth conditions strongly affect the composition of the secretome.
    Yeast 08/2010; 27(8):661-72. DOI:10.1002/yea.1775 · 1.74 Impact Factor
Show more