Candida albicans gastrointestinal colonization and invasive filamentation
Herwald, Sanna.
2017
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Abstract: Candida albicans is an opportunistic fungal pathogen that is a
common commensal colonizer of the human gastrointestinal (GI) tract, but in
immunocompromised hosts can cause life-threatening candidemia. Interestingly, Candida GI
tract colonization is the main source of C. albicans found in candidemia. Previous studies
showed that long-term murine GI tract colonization with C. albicans... read morecauses a host-specific,
possibly immunologic, change that results in a GI tract environment that is more
restrictive to C. albicans cells. Further, C. albicans EFG1 was the first gene for which
expression was shown to vary in colonizing C. albicans cells depending on host immune
status. A restrictive GI tract environment is more restrictive to C. albicans cells lacking
the gene EFG1 than to wild-type C. albicans cells. We examined the transcript levels of
known regulators of EFG1 transcription and activity in C. albicans colonizing mice of
different immune status. We found differential expression of genes encoding most components
that function in the same filamentation pathway as EFG1, and genes encoding components of
histone-modifying complexes involved in EFG1 regulation. Therefore, host immune status
causes extensive changes in the transcription patterns of colonizing C. albicans. We also
demonstrated that a specific portion of the murine host immune system, CD4+ cells, is
required for the maintenance of the restrictive phenotype against colonizing efg1 null
cells in long-term C. albicans-colonized mice. Therefore, we have identified specific
changes to the host immune system that either result from C. albicans colonization of the
GI tract or alter the fitness of colonizing C. albicans. Additionally, we found that GI
colonization by C. albicans dramatically increases gastric transcript levels of murine
cytokines IL-22 and IL-17, but not IL-10 or IFN-γ. During infection C. albicans forms
invasive filaments that invade the tissue of its host. The glycosylated, integral plasma
membrane protein Dfi1 is important for invasive filamentation in a laboratory model. In
this thesis, we show that Dfi1 remains an integral membrane protein despite deletion of
either of its two predicted transmembrane domains, whereas deletion of both domains results
in a soluble protein. Additionally, properly-oriented Dfi1, as indicated by N-linked
glycosylation, was observed when either transmembrane domain was deleted, but was absent
when both transmembrane domains were deleted. Finally, Dfi1 lacking the N-terminal
transmembrane domain was observed at the cell periphery, whereas the double-deletion mutant
was diffusely intracellular. Therefore, Dfi1 contains two transmembrane domains which
contribute to its biogenesis.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Molecular Microbiology.
Advisor: Carol Kumamoto.
Committee: Claire Moore, Gavin Schnitzler, and Honorine Ward.
Keyword: Microbiology.read less - ID:
- nk322r88f
- Component ID:
- tufts:23395
- To Cite:
- DCA Citation Guide EndNote
