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Updated: May 11, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Differential virulence of Candida glabrata glycosylation mutants
Lara West1, Douglas W Lowman, Héctor M Mora-Montes
1Department of Microbiology, Imperial College London, London, SW7 2AZ, United Kingdom.
Abstract:
The fungus Candida glabrata is an important and increasingly common pathogen of humans, particularly in immunocompromised hosts. Despite this, little is known about the attributes that allow this organism to cause disease or its interaction with the host immune system. However, in common with other fungi, the cell wall of C. glabrata is the initial point of contact between the host and pathogen, and as such, it is likely to play an important role in mediating interactions and hence virulence. Here, we show both through genetic complementation and polysaccharide structural analyses that C. glabrata ANP1, MNN2, and MNN11 encode functional orthologues of the respective Saccharomyces cerevisiae mannosyltransferases. Furthermore, we show that deletion of the C. glabrata Anp1, Mnn2, and Mnn11 mannosyltransferases directly affects the structure of the fungal N-linked mannan, in line with their predicted functions, and this has implications for cell wall integrity and consequently virulence. C. glabrata anp1 and mnn2 mutants showed increased virulence, compared with wild-type (and mnn11) cells. This is in contrast to Candida albicans where inactivation of genes involved in mannan biosynthesis has usually been linked to an attenuation of virulence. In the long term, a better understanding of the attributes that allow C. glabrata to cause disease will provide insights that can be adopted for the development of novel therapeutic and diagnostic approaches.
Insights
Candida glabrata mannosyltransferase gene deletions (anp1, mnn2) unexpectedly increased fungal virulence. This contrasts with Candida albicans and highlights distinct mechanisms in fungal pathogenesis.
Area of Science:
- Mycology
- Medical Mycology
- Molecular Biology
Background:
- Candida glabrata is a significant human pathogen, especially in immunocompromised individuals.
- Understanding its virulence factors and host interactions is crucial for developing new therapies.
- The fungal cell wall is a key interface for host-pathogen interactions.
Purpose of the Study:
- To investigate the role of mannosyltransferases (ANP1, MNN2, MNN11) in Candida glabrata cell wall mannan structure and virulence.
- To compare the function of these genes in C. glabrata with their orthologues in Saccharomyces cerevisiae.
Main Methods:
- Genetic complementation assays were used to confirm gene function.
- Polysaccharide structural analyses were performed to determine the impact on N-linked mannan.
- Virulence was assessed in vivo by comparing mutant strains to wild-type C. glabrata.
Main Results:
- ANP1, MNN2, and MNN11 were identified as functional mannosyltransferases in C. glabrata.
- Deletion of ANP1 and MNN2 genes altered N-linked mannan structure and cell wall integrity.
- C. glabrata anp1 and mnn2 mutants exhibited increased virulence compared to wild-type strains, contrary to findings in Candida albicans.
Conclusions:
- Mannosyltransferases play a critical role in shaping the C. glabrata cell wall mannan.
- The disruption of mannan biosynthesis in C. glabrata can enhance virulence, offering a novel perspective on fungal pathogenesis.
- Further research into C. glabrata virulence attributes can inform the development of targeted therapeutic and diagnostic strategies.
