An Investigation of the Extracellular Region of Dfi1 Protein in Candida albicans
Pugliese, Antonia.
2019
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Candida albicans is
a polymorphic yeast which grows as a commensal organism in much of the population. While
most carriage is asymptomatic, C. albicans also functions as an opportunistic pathogen
in immunocompromised patients, contributing to painful mucosal infections as well as
life-threatening candidemia. This transition in lifestyle of the yeast is linked to a
morphological transition to ... read moregrowth in the filamentous form. One factor that can
influence the transition to filamentous growth, and which is related to pathogenicity in
mice, is the Dfi1-dependent sensing of growth in contact with a surface. The Dfi1
protein is structured with two trans-membrane regions, with an extracellular region in
between, and the C-terminal and N-terminal tails facing into the cell. The C-terminal
tail is known to interact with calmodulin, and to be necessary to set off a kinase
cascade in response to growth in contact with agar which includes the activation by
phosphorylation of the MAP kinase Cek1. The extracellular region contains a section rich
in serine and threonine residues, and Dfi1 is known to be heavily glycosylated with N-
and O-linked glycosylations. The extracellular region also contains a highly conserved
region, with high sequence homology to Dfi1-homologues in related Candida species. The
importance of these extracellular regions was interrogated using four deletion mutants
that lacked between 36-66 amino acids from the Dfi1 protein. The results of this project
show that the highly conserved region of this domain is involved in Dfi1-dependent
filamentation, as well as activation of Cek1 in response to Caspofungin and subsequent
resistance to low levels of the anti-fungal drug. The serine threonine rich region of
this domain is important for filamentation, but does not contribute to resistance to
Caspofungin.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Molecular Microbiology.
Advisor: Carol Kumamoto.
Committee: Andrew Camilli, Joan Mecsas, Abraham Sonnenshein, and Wai-Leung Ng.
Keyword: Molecular biology.read less - ID:
- kp78gv32n
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