Status | 已發表Published |
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 Publication | Microbial Pathogenesis & Host Response |
Abstract | Candida 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. |
Keyword | Candida glabrata Xbp1 transcription host |
Language | 英語English |
The Source to Article | PB_Publication |
PUB ID | 39963 |
Document Type | Conference paper |
Collection | DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences |
Corresponding Author | Wong, 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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