Molecular Mycology

Research interest

The research in our Molecular Mycology group aims at getting a better understanding of the molecular processes that underlie the establishment of fungal infections in humans. Especially infections caused by fungal pathogens such as Candida albicans and related species occur frequently and pose an important problem to human societies. In immunocompromised patients, Candida may cause systemic bloodstream infections which are life-threatening and difficult to diagnose and treat. Therefore, better methods for prevention, diagnosis and treatment are urgently needed.

Fungal cell walls are extremely strong macromolecular structures that shape the cells and enable them to resist the internal turgor pressures, and at the same time protect the cells against hazardous molecules in the surrounding environment. Being the interface between fungus and host, the cell wall of pathogenic fungi is an obvious target for the development of novel antifungals.

In most cases, the fungal cell wall matrix is composed of covalently-linked polysaccharides and proteins. The outer mannoprotein layer harbors a wide diversity of differentially regulated proteins that are implicated various aspects of the infection process. Part of our research is aimed to elucidate the role of these cell wall proteins in the primary host-fungus interactions leading to adhesion, biofilm formation and virulence.

We are also interested in elucidating the molecular mechanisms that underlie the biosynthesis of the fungal cell wall. Ample knowledge is available concerning the synthesis of individual cell wall components, however, how these molecules become crosslinked to yield a strong macromolecular matrix is largely unknown. The work in our group therefore is aimed also at the identification and characterization of extracellular enzymes that are involved in crosslinking individual cell wall components into a macromolecular network.

Post-genomic approaches have a prominent place in our research, as well as functional characterization of important cell surface proteins, such as carbohydrate-active enzymes and adhesins, through phenotypic analyses of deletion mutants and overexpression studies. Post-genomic approaches include bioinformatics/comparative genomics, quantitative proteomics (mass spectrometry), and transcript profiling. We further employ microbiological techniques (cell culturing, biofilms, virulence models, cell imaging techniques) and biochemical methods (protein separation, sugar analysis).

Students interested in doing an internship in our group can contact Dr. Piet de Groot (Piet.deGroot@uclm.es).

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Funding

  • Título: Identificación y caracterización de proteínas de pared celular relevantes en la infección por Candida mediante el desarrollo de nuevas estrategias terapéuticas para el control de infecciones fúngicas
    Entidad financiadora: Consejería de Educación, Cultura y Deportes
    I.P.: Piet de Groot
    Duración, desde: 27/09/2014   hasta: 26/09/2016
  • Título: Importancia de las adhesinas de Candida Glabrata en la interacción huesped-patógeno, desarrollo de candidiasis y de nuevas terápias antifíngicas
    Entidad financiadora: Ministerio de Economía y Competitividad
    I.P.: Piet de Groot
    Duración, desde: 01/01/2014   hasta: 31/12/2015
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Publications

  • Proy-Vega B, Aguirre C, de Groot P, Solís-García del Pozo J, Jordán J. On the clinical evidence leading to tetrazepam withdrawal. Expert Opin Drug Saf. 2014; 13(6):705-12. doi: 10.1517/14740338.2014.915023.. (A).
  • Solís-García Del Pozo J, Mínguez-Mínguez S, de Groot PWJ, Jordán J. Rasagiline meta-analysis: a spotlight on clinical safety and adverse events when treating Parkinson’s disease. Expert Opin Drug Saf. 2013; 12(4): 479-486. (A).
  • de Groot PWJ, Bader O, de Boer AD, Weig M, Chauhan N. Adhesins in human fungal pathogens: glue with plenty of stick. Eukariot Cell. 2013; 12 (4): 470-481. (A).
  • Gioti A, Nystedt B, Li W, Xu J, Andersson A, Averette AF, Münch K, Wang X, Kappauf C, Kingsbury JM, Kraak B, Walker LA, …, De Groot PWJ, Butler G, Heitman J, Scheynius A. Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis. Mbio. 2013; 4(1): e00572-12. (A).
  • Karachitos A, Del Pozo JS, de Groot PWJ, Kmita H, Jordán J. Minocycline as Cytoprotective Drug: Implications for Therapy of Cerebrovascular and Neurodegenerative Diseases. Curr Drug Targets. 2013; 14: 47-55. [Epub 2012]. (A).
  • De Groot PWJ, Martinez AI, Castillo L. A genomic inventory of cell wall biosynthesis in the ubiquitous plant pathogen Botrytis cinerea. En: The Fungal Cell Wall (Mora-Montes HM, Ed.). 2013. ISBN: 978-1-62618-266-0. Ed. Nova Science Publishers, Inc (Hauppauge, NY, EE.UU.). [Epub 2012]. (CL).
  • Wagener J, Weindl G, De Groot PWJ, De Boer AD, Kaesler S, Thavaraj S, Bader O, Mailänder-Sanchez D, Borelli C, Weig M, Biedermann T, Naglik JR, Korting HC, Schaller M. Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells. PLoS One. 2012; 7(11): e50518. (A).
  • Bader O, Schwarz A, Kraneveld EA, Tangwattanchuleeporn M, Schmidt P, Jacobsen MD, Groß U, De Groot PWJ, Weig M. Gross Karyotypic and Phenotypic Alterations among Different Progenies of the Candida glabrata CBS138/ATCC2001 Reference Strain. PLoS One. 2012; 7(12): e52218. (A).
  • Thevissen K, de Mello Tavares P, Xu D, Blankenship J, Vandenbosch D, Idkowiak-Baldys J, Govaert G, Bink A, Rozental S, De Groot PWJ, Davis TR, Kumamoto CA, Vargas G, Nimrichter L, Coenye T, Mitchell A, Roemer T, Hannun YA, Cammue BP. The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans. Mol Microbiol. 2012. 84[1]: 166-180. (A).
  • Gelis S, de Groot PWJ, Castillo L, Moragues MD, Sentandreu R, Gómez MM, Valentín E. Pga13 in Candida albicans is localized in the cell wall and influences cell surface properties, morphogenesis and virulence. Fungal Genet Biol. 2012. 49[4]: 322-331. (A).
  • de Groot PWJ, Brandt BW. ProFASTA: A pipeline web server for fungal protein scanning with integration of cell surface prediction software. Fungal Genet Biol. 2012. 49[2]: 173-179. (A).
  • de Groot PWJ, Brul s, Klis FM. Exploring the fungal wall glycoproteome. En: Glycosylation in Diverse Cell Systems: Challenges and New Frontiers in Experimental Biology (Brooks S et al, Eds. Essential Reviews in Experimental Biology, Vol. 4). 2011. ISBN: 978-1-907491-06-1. Ed. Society for Experimental Biology (London, UK). (CL).
  • Kraneveld EA, de Soet JJ, Deng DM, Dekker HL, de Koster CG, Klis FM, Crielaard W, de Groot PWJ. Identification and Differential Gene Expression of Adhesin-Like Wall Proteins in Candida glabrata Biofilms. Mycopathologia. 2011. 172[6]: 415-427. (A).
  • Jordan J, de Groot PWJ, Galindo MF. Mitochondria: The Headquarters in Ischemia-Induced Neuronal Death.Cent Nerv Syst Agents Med Chem. 2011. 11[2]: 98-106. (A).
  • Laforet L, Moreno I, Sánchez-Fresneda R, Martínez-Esparza M, Martínez JP, Argüelles JC, de Groot PWJ, Valentín E. Pga26 mediates filamentation and biofilm formation and is required for virulence in Candida albicans. FEMS Yeast Res. 2011. 11: 389-397. (A).
  • Sosinska GJ, de Koning LJ, de Groot PWJ, Manders EM, Dekker HL, Hellingwerf KJ, de Koster CG, Klis FM. Mass spectrometric quantitation of the adaptations in the wall proteome of Candida albicans in response to ambient pH. Microbiology. 2011. 157: 136-146. [Epub 2010]. (A).
  • Schild L, Heyken A, de Groot PWJ, Hiller E, Mock M, de Koster C, Horn U, Rupp S, Hube B. Proteolytic cleavage of covalently linked cell wall proteins by Candida albicans Sap9 and Sap10. Eukaryot Cell. 2011. 10: 98-109. [Epub 2010]. (A).
  • Van der Klei I, Veenhuis M, Klis FM, De Groot PWJ, Brul S, Müller WH, Van Driel KGA, Boekhout T. Cytology, septa and cell walls: a summary of yeast cell biology in phylogenetic perspective. En: The Yeast 5th ed. (Kurtzman, Fell, Boekhout, Eds.). 2011. Págs: 111-128. ISBN: 978-0-444-52149-1. Ed. Elsevier Sciencie (Amsterdam, Holanda). (CL).
  • de Boer AD, de Groot PWJ, Weindl G, Schaller M, Riedel D, Diez-Orejas R, Klis FM, de Koster CG, Dekker HL, Gross U, Bader O, Weig M. The Candida albicans cell wall protein Rhd3/Pga29 is abundant in the yeast form and contributes to virulence. Yeast. 2010. 27[8]: 611-624. (A).
  • Yin QY, de Groot PWJ, Dekker HL, de Jong L, Klis FM, de Koster CG. Comprehensive proteomic analysis of Saccharomyces cerevisiae cell walls: identification of proteins covalently attached via glycosylphosphatidylinositol remnants or mild alkali-sensitive linkages. J Biol Chem. 2005. 280[21]: 20894-20901. (A).

Piet de Groot

Director

People

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Phone: (+34) 967 599 200

Contact information

Centro Regional de Investigaciones Biomédicas

Universidad de Castilla-La Mancha

C/ Almansa, 14.

02008 Albacete (España)

telefono (-34) 967 599 200, Ext. 2889

fax (+34) 967 599 360

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