1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease

Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance

  1. Maruti Nandan Rai
  2. Qing Lan
  3. Chirag Parsania
  4. Rikky Rai
  5. Niranjan Shirgaonkar
  6. Ruiwen Chen
  7. Li Shen
  8. Kaeling Tan
  9. Koon Ho Wong  Is a corresponding author
  1. University of Macau, Macao
https://doi.org/10.7554/eLife.73832
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  1. Maruti Nandan Rai
  2. Qing Lan
  3. Chirag Parsania
  4. Rikky Rai
  5. Niranjan Shirgaonkar
  6. Ruiwen Chen
  7. Li Shen
  8. Kaeling Tan
  9. Koon Ho Wong
(2024)
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
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  3. Download .RIS

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.

The following data sets were generated

Article and author information

Author details

  1. Maruti Nandan Rai

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  2. Qing Lan

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  3. Chirag Parsania

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  4. Rikky Rai

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  5. Niranjan Shirgaonkar

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6078-1409

  6. Ruiwen Chen

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  7. Li Shen

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  8. Kaeling Tan

    Faculty of health sciences, University of Macau, Taipa, Macao
    Competing interests
    The authors declare that no competing interests exist.

  9. Koon Ho Wong

    Faculty of health sciences, University of Macau, Taipa, Macao
    For correspondence
    koonhowong@um.edu.mo
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9264-5118

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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  1. Maruti Nandan Rai
  2. Qing Lan
  3. Chirag Parsania
  4. Rikky Rai
  5. Niranjan Shirgaonkar
  6. Ruiwen Chen
  7. Li Shen
  8. Kaeling Tan
  9. Koon Ho Wong
(2024)
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

Share this article

https://doi.org/10.7554/eLife.73832

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