Candida albicans gastrointestinal colonization and invasive filamentation
Herwald, Sanna.
2017
-
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 cau... read moreses 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
- To Cite:
- DCA Citation Guide EndNote
