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Candida glabrata Xbp1 represses early transcription response during interaction with host macrophages
Rai, N.; Parsania, C.; Rai, R.; Wong, K. H.
2017-09-12
Source PublicationMicrobial Pathogenesis & Host Response
AbstractCandida glabrata, an opportunistic human fungal pathogen in immunocompromised patients, remodels its carbon metabolism to survive in nutrient-deprived intracellular macrophage microenvironment. Here, we have identified a transcription factor, CgXbp1, required for remodeling carbon metabolic pathways in C. glabrata upon exposure to host macrophages. Employing the next generation sequencing approaches, we showed that Cgxbp1Δ mutant exhibited constitutively active fatty acid catabolic and proteolytic pathways even in the presence of sufficient carbohydrate in the growth medium, suggesting that carbon metabolic processes are deregulated upon CgXBP1 deletion. Next, we demonstrated that CgXbp1 is essential for arresting the cells in G1 phase of cell cycle during carbon starvation. Global gene expression analysis on Cgxbp1Δ mutant revealed that genes associated with GO terms – mitochondrion organization, mitochondrial transport and mitochondrial translation were highly enriched among down-regulated genes, indicating that CgXbp1 may have pivotal roles in cellular energy homeostasis maintenance. Comparison of the transcriptional profiles of macrophage-engulfed wild-type and Cgxbp1Δ mutant cells revealed that unlike wild-type cells, Cgxbp1Δ mutant was unable to repress genes associated with GO terms - Translation, Ribosome biogenesis and RNA metabolic processes during early stage of macrophage infection. Finally, we performed time-course gene expression analyses in C. glabrata cells after phagocytosis by THP-1 macrophages, and demonstrated that Cgxbp1Δ mutant affects the temporal transcriptional response to macrophages. Overall, our data established that CgXbp1 is central in carbon metabolic remodeling during host-pathogen interactions in C. glabrata.
KeywordCandida glabrata Xbp1 transcription host
Language英語English
The Source to ArticlePB_Publication
PUB ID39963
Document TypeConference paper
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Faculty of Health Sciences
Corresponding AuthorWong, K. H.
Recommended Citation
GB/T 7714
Rai, N.,Parsania, C.,Rai, R.,et al. Candida glabrata Xbp1 represses early transcription response during interaction with host macrophages[C], 2017.
APA Rai, N.., Parsania, C.., Rai, R.., & Wong, K. H. (2017). Candida glabrata Xbp1 represses early transcription response during interaction with host macrophages. Microbial Pathogenesis & Host Response.
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