Elucidating the role of the AP2 endocytic adaptor complex on C.albicans virulence.

Lead Research Organisation: University of Sheffield
Department Name: Biomedical Science

Abstract

We have deleted an essential subunit of the AP2 endocytic adaptor complex in Candida albicans, and observed marked defects in polarised growth. As shown previously, the apm4 deletion mutant is unable to form long, thin filamentous cells under inducing conditions, instead growing wide and misshapen hyphae. The mutant is only slightly impaired in fluid phase endocytosis, leading us to hypothesise that AP2 plays a role in the endocytosis of specific cargoes which are important to polarised growth. It has recently become clear that a balance of endocytosis and secretion is essential for the highly polarised growth seen in filamentous fungi, however many of the key players remain unknown (Schultzhaus and Shaw, 2017). This polarised growth is a key aspect of cell biology, and is also central to Candida albicans virulence (Mayer et al., 2013). Therefore, elucidating the role of the AP2 endocytic adaptor complex in hyphal growth and virulence of Candida albicans is of great importance.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1660283 Studentship BB/M011151/1 30/09/2015 29/09/2019 Harriet Constance Knafler
 
Description My first project on this grant was: nanoparticle uptake in S.cerevisiae. I worked on this for around 8 months, and found that these specific polymersome nanoparticles were not in fact being endocytosed by yeast, as we thought they were. It was just the dye we were seeing entering the yeast cells, and the larger nanoparticles were not entering the cells. This was a negative result, and resulted in my phD project being changed as we could not move forward with this. My new project for the last 2 years has been: elucidating the role of the AP2 endocytic adaptor complex in Candida albicans virulence. I have discovered that AP2 is required for trafficking of the cell wall biosynthesis enzyme Chs3. I have shown this lead to many defects in cell wall regulation, and in polarised hyphal growth. This is a key example to show that the trafficking of particular cargoes in fungi can have far reaching effects on morphology and virulence. It is also evidence to support a cargo specific role for AP2 in yeast.
Exploitation Route The next steps to these findings could be searching for more AP2 cargoes - we have found one but there are likely to be many more. These could be found by a screen for example. Our lab is also hoping to take this project forwards by finding a more detailed mechanism of how Chs3 is internalised by AP2.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Candida cell wall analysis 
Organisation University of Aberdeen
Department Aberdeen Fungal Group
Country United Kingdom 
Sector Academic/University 
PI Contribution We made candida yeast strains
Collaborator Contribution Our yeast strains were analysed by HPLC and electron microscopy at the University of Aberdeen fungal group The project and other appropriate experiments were also discussed
Impact Paper in press at mBio (no PMID at this point)
Start Year 2017