Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance
- University of Macau, Macao
Abstract
Candida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects fluconazole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabrata's survival in macrophages and drug tolerance.
Data availability
RNAPII ChIP-seq, CgXbp1MYC ChIP-seq and RNAseq data are available from the NCBI SRA database under the accession number PRJNA665114, PRJNA743592 and PRJNA1162247, respectively.
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Candida glabrata infection of THP1 macrophagesNCBI BioProject, PRJNA665114.
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ChIPseq analysis of Xbp1 in Candida glabrataNCBI BioProject, PRJNA743592.
Article and author information
Author details
Niranjan Shirgaonkar
Funding
Research Services and Knowledge Transfer Office, University of Macau (MYRG2019-00099-FHS)
- Koon Ho Wong
Fundo para o Desenvolvimento das Ciências e da Tecnologia (0033/2021/A1)
- Koon Ho Wong
Research Services and Knowledge Transfer Office, University of Macau (MYRG2022-00107-FHS)
- Koon Ho Wong
Fundo para o Desenvolvimento das Ciências e da Tecnologia (0099/2022/A2)
- Koon Ho Wong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Rai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance
eLife 13:e73832.
https://doi.org/10.7554/eLife.73832
