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Updated: Jul 12, 2025

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata
Qi Ni1, Xianwei Wu2, Tongxuan Su1
1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197 Ruijin ER Road, Shanghai, 200025, China.
Background:
Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection. Although coping with the induced DNA damage is widely acknowledged to be important, the underlying mechanisms remain unclear.
Results:
The present study provides hitherto undocumented evidence of the importance of the regulatory subunits of CgCK2 (CgCkb1 and CgCkb2) in response to DNA damage. Deletion of CgCKB1 or CgCKB2 enhanced cellular apoptosis and DNA breaks and led to cell cycle delay. In addition, deficiencies in survival upon phagocytosis were observed in Δckb1 and Δckb2 strains. Consistently, disruption of CgCKB1 and CgCKB2 attenuated the virulence of C. glabrata in mouse models of invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 and CgCkb2 participate in cell cycle resumption and genomic stability.
Conclusions:
Overall, our findings suggest that the response to DNA damage stress is crucial for C. glabrata to survive in macrophages, leading to full virulence in vivo. The significance of this work lies in providing a better understanding of pathogenicity in C. glabrata-related candidiasis and expanding ideas for clinical therapies.
Insights
Regulatory subunits CgCKB1 and CgCKB2 are vital for Candida glabrata
Area of Science:
- Microbiology
- Molecular Biology
- Mycology
Background:
- Candida glabrata is a prevalent opportunistic pathogen known for drug resistance.
- C. glabrata evades host immunity, leading to persistent infections.
- Mechanisms of C. glabrata's DNA damage response are not fully understood.
Purpose of the Study:
- Investigate the role of CgCK2 regulatory subunits (CgCkb1, CgCkb2) in DNA damage response.
- Determine the impact of CgCKB1 and CgCKB2 on C. glabrata virulence and survival.
Main Methods:
- Gene deletion studies (Δckb1, Δckb2 strains).
- Analysis of cellular apoptosis and DNA breaks.
- Phagocytosis survival assays.
- Murine models of invasive candidiasis.
- Global transcriptional profiling.
Main Results:
- Deletion of CgCKB1 or CgCKB2 increased apoptosis and DNA breaks.
- Δckb1 and Δckb2 strains showed reduced survival after phagocytosis.
- Disruption of CgCKB1/CgCKB2 attenuated virulence in vivo.
- CgCkb1 and CgCkb2 are involved in cell cycle resumption and genomic stability.
Conclusions:
- DNA damage response is critical for C. glabrata survival in macrophages and virulence.
- CgCKB1 and CgCKB2 are key regulators of DNA damage response and virulence.
- Findings enhance understanding of candidiasis pathogenicity and suggest therapeutic targets.
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