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Published on: October 18, 2017
COS-l, a putative two-component histidine kinase of Candida albicans, is an in vivo virulence factor
C P Selitrennikoff1, L Alex, T K Miller
1University of Colorado Health Sciences Center, Department of Cellular and Structural Biology, Denver 80262, USA. claude.selitrennikoff@uchsc.edu
Abstract:
The human fungal pathogen, Candida albicans, has three putative histidine kinases showing homology to those of plants, bacteria and other fungi. We have constructed a homozygous deletion strain and a hemizygous reconstituted strain of one of these histidine-kinase-encoding genes, COS-1, in C. albicans. Neither strain showed any growth defect in a number of liquid media nor increased resistance or sensitivity to a number of antifungal drugs. Importantly, we show that the COS-1 homozygous disruption strain had significantly reduced virulence in a systemic murine model of candidosis. Thus, COS-1 appears to be an in vivo virulence factor and may represent a novel target for the development of antifungal drugs.
Insights
Candida albicans COS-1 gene disruption reduced its virulence in mice, suggesting it is a key factor for fungal infection and a potential target for new antifungal drugs.
Area of Science:
- Medical Mycology
- Molecular Biology
- Pathogen Virulence
Background:
- Candida albicans is a major human fungal pathogen.
- Histidine kinases are crucial signaling molecules in fungi, plants, and bacteria.
- Understanding C. albicans virulence factors is key to developing new antifungal therapies.
Purpose of the Study:
- To investigate the role of the histidine kinase gene COS-1 in Candida albicans.
- To determine if COS-1 is essential for fungal growth or drug resistance.
- To evaluate the contribution of COS-1 to C. albicans virulence in a mammalian model.
Main Methods:
- Construction of homozygous deletion and hemizygous reconstituted strains of the COS-1 gene in C. albicans.
- Assessment of fungal growth in various liquid media.
- Testing antifungal drug resistance and sensitivity.
- Evaluation of virulence in a systemic murine model of candidosis.
Main Results:
- The COS-1 deletion and reconstituted strains showed no growth defects in liquid media.
- No altered resistance or sensitivity to antifungal drugs was observed.
- The COS-1 homozygous disruption strain exhibited significantly reduced virulence in the murine candidosis model.
Conclusions:
- The COS-1 gene is not essential for C. albicans growth or antifungal drug response.
- COS-1 is an important in vivo virulence factor for C. albicans.
- COS-1 represents a potential novel target for developing new antifungal drugs.
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