Show simple item record

Characterization of the cell wall protein Ecm33 family in Candida glabrata

dc.contributor.advisorWeig, Michael PD Dr.
dc.contributor.authorTangwattanachuleeporn, Marut
dc.titleCharacterization of the cell wall protein Ecm33 family in Candida glabratade
dc.contributor.refereeGroß, Uwe Prof. Dr.
dc.description.abstractengCandida glabrata is the second most frequent cause of local and systemic human candidiasis and infections with this species are difficult to treat because of frequent azole resistance. C. glabrata infections have high mortality rates in immunocompromised patients. During pathogenesis, the cell wall is of particular importance, because it holds key functions such as adhesion and countering of immune defenses. Next to the structural proteins of the Cwp1-family, Ecm33 and Pst1 have been identified as the most abundant GPI-anchored proteins in the cell wall, but their functions are largely unclear. In C. albicans and S. cerevisiae, the ECM33 deletion mutants show partially overlapping phenotypes suggesting defects in cell wall assembly. Therefore, gene disruption and complementation experiments were conducted on these genes in C. glabrata. The results of these experiments show that, similar to C. albicans and S. cerevisiae, the C. glabrata ∆ecm33 and ∆pst1/∆ecm33 mutants are susceptible to most cell wall perturbing agents. The mutants have a more negatively charged cell wall surface and release Cwp1 protein and β-1,6-glucan containing material to the environment. Most importantly, as a consequence the mutants lose some adherence capacities, which is of particular interest in terms of C. glabrata pathogenicity. With the notable exceptions of the adherence phenotype and the surface charge, the phenotypes are rescued by introduction of ScECM33 and CaEMC33. In contrast, the phenotypes could not be compensated in the ∆ecm33 mutant of C. glabrata by overexpression of the remaining members of the C. glabrata ECM33-family (CgPST1, CgSPS2 and CgSPS22). However, we can not rule out that this is due to technical limitations of the experimental approaches. From the overall phenotypic data, we can propose that Ecm33 probably is involved in the linkage of β-1,6-glucan to the cell wall. If β-1,6-glucan is lost, so is its carrier function for effector proteins, resulting in the observed phenotypes. The generated phenotypic data also enabled to develope different hypothetical models for the biological function of Ecm33 in C. glabrata and the functional analyses performed so far indicate that CgEcm33 might be a lectin. These analyses now make it possible to further characterize the biological role of this very abundant cell wall protein, for example using comprehensive binding assays, glycochip experiments and proteomic work on the cell wall and secreted proteomes of the generated mutants. The improved understanding of the cell wall in C. glabrata will enable to characterize pathogenicity in this organism and potentially develop new antifungal
dc.contributor.coRefereeBraus, Gerhard Prof. Dr.
dc.subject.engEcm33 proteinde
dc.subject.engCandida glabratade
dc.subject.engCell wall proteinde
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de

Files in this item


This item appears in the following Collection(s)

Show simple item record