The University of Sheffield
Department of Molecular Biology and Biotechnology

Cellular morphogeneisis in the human pathogen Candida albicans


Prof P E Sudbery - Roper Chair in Genetics

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This pathogenic fungus is responsible for thrush and candidiasis a lethal infection common in immuno-compromised patients. After MRSA, it is probably the second most common cause of death from hospital acquired infections It can grow in a variety of morphogenic forms ranging from unicellular yeast, chains of elongated cells known as pseudohyphae and finally true hyphae consisting of long tubes with parallel sides. These different morphogenic forms are thought to be important in the infective process. We are studying the mechanisms that remodel cell growth during the formation of hyphae and pseudohyphae from unbudded yeast cells. Our strategy has been to employ a combination of molecular genetics and high resolution fluorescence microscopy. We use model organisms such as Saccharomyces cerevisiae and Aspergillus nidulans to guide our research, but we often find that there are important differences in the way the mechanisms operate in C. albicans compared to these model organisms

 

Localisation of Myosin light chain (Mlc1) in developing hyphae of C. albicans We have identified a structure at the growing tip of hyphae which drives the polarized growth from the tip. This picture shows the localisation of a protein called Myosin light chain (Mlc1) in developing hyphae. This protein has been visualised by fusion to YFP. It localises to the Spitzenkörper forming a discrete yellow spot at the tips. The cell walls have been stained blue with Calcofluor. (Scale bar 10mm)

 

Selected Publications

Sudbery, P.E. (2007) Morphogenesis of a human fungal pathogen requires septin phosphorylation. Developmental Cell 13:315-316
Sudbery, P.E. and Court, H. (2007) Polarised growth in Fungi In: The Mycota VIII, 2 edition. Biology of the fungal cell. ed. R.J.Howard and N.A.R.Gow. Berlin: Springer-Verlag, 137-166.
Court, H. and Sudbery, P.E. (2007) Regulation of Cdc42 GTPase activity in the formation of hyphae in Candida albicans. Molecular Biology of the Cell 18:265-281
Crampin, H., Finley, K., Gerami-Nejad M., Court H., Gale C., Berman, J. and P.E.Sudbery. (2005). Candida albicans hyphae have a Spitzenk&oumlrper that is distinct from the polarisome found in yeast and pseudohyphae. Journal of Cell Science 118:2935-2947.
Chapa y Lazo, B., Bates, S., Sudbery, P.E. (2005) The G1 cyclin, Cln3, regulates morphogenesis in Candida albicans. Eukayrotic Cell 4(1) 90-94
Sudbery, P.E., Gow, N.A.R. and Berman, J. (2004) The distinct morphological states of Candida albicans. Trends in Microbiology. 12:317-324
Wightman, R. Bates, S. Amornorrattanapan, P and Sudbery, P.E. (2004) In Candida albicans, the Nim1 kinases Gin4 and Hsl1 negatively regulate pseudohypha formation and Gin4 also controls septin organization. Journal of Cell Biology. 164:581-591
Care, A, Vousden, K.A., Binley, K.M., Radcliffe, P.R. Trevethick, J, Mannazzu, I. and Peter E. Sudbery. (2004) A synthetic lethal screen identifies a role for the cortical actin patch/endocytosis complex in the control of cell division in yeast. Genetics. 166: 707-719
Martínez-Anaya,C., J.R.Dickinson, and P.E.Sudbery. (2003). In yeast, the pseudohyphal phenotype induced by isoamyl alcohol results from the operation of the morphogenesis checkpoint. Journal of Cell Science. 116:3423-3431
Berman,J. and Sudbery,P.E. (2002). Candida albicans : A molecular revolution built on lessons from budding yeast. Nature Reviews Genetics 3, 918-930.
Sudbery P.E. (2002) When Whi meets wee. Science 297:351-2
Sudbery, P.E. (2001) The germ tubes of Candida albicans hyphae and pseudohyphae show different patterns of septin ring localisation. Molecular Microbiology. 41 19-31
Leng, P. Sudbery P.E. and Brown, A.J.P. (2000) Rad6p represses yeast hyphal morphogenesis. Molecular Microbiology 35 1-13
Care, R.S. Trevethick, J. Binley K.M and Sudbery P.E. (1999) The MET3 promoter: a new tool for Candida albicans molecular genetics. Molecular Microbiology 34:792-798Reviews Genetics 3, 918-930.