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Characterization of Virulence-Related Phenotypes in Candida Species of the CUG Clade
Shelby J Priest1, Michael C Lorenz2
1Department of Microbiology and Molecular Genetics and the Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA.
Abstract:
Candida species cause a variety of mucosal and invasive infections and are, collectively, the most important human fungal pathogens in the developed world. The majority of these infections result from a few related species within the "CUG clade," so named because they use a nonstandard translation for that codon. Some members of the CUG clade, such as Candida albicans, present significant clinical problems, whereas others, such as Candida (Meyerozyma) guilliermondii, are uncommon in patients. The differences in incidence rates are imperfectly correlated with virulence in animal models of infection, but comparative analyses that might provide an explanation for why some species are effective pathogens and others are not have been rare or incomplete. To better understand the phenotypic basis for these differences, we characterized eight CUG clade species--C. albicans, C. dubliniensis, C. tropicalis, C. parapsilosis, Clavispora lusitaniae, M. guilliermondii, Debaryomyces hansenii, and Lodderomyces elongisporus--for host-relevant phenotypes, including nutrient utilization, stress tolerance, morphogenesis, interactions with phagocytes, and biofilm formation. Two species deviated from expectations based on animal studies and human incidence. C. dubliniensis was quite robust, grouping in nearly all assays with the most virulent species, C. albicans and C. tropicalis, whereas C. parapsilosis was substantially less fit than might be expected from its clinical importance. These findings confirm the utility of in vitro measures of virulence and provide insight into the evolution of virulence in the CUG clade.
Insights
This study compared virulence traits of eight Candida species. Candida dubliniensis showed high virulence, while Candida parapsilosis was less fit, challenging previous assumptions about fungal pathogen evolution.
Area of Science:
- Medical Mycology
- Evolutionary Biology
- Pathogen Phenomics
Background:
- Candida species are major human fungal pathogens, with CUG clade members causing most infections.
- Clinical incidence of CUG clade species doesn't perfectly correlate with animal model virulence.
- Comparative phenotypic analyses explaining virulence differences are lacking.
Purpose of the Study:
- To investigate the phenotypic basis for varying virulence among eight CUG clade Candida species.
- To compare host-relevant phenotypes including nutrient utilization, stress tolerance, morphogenesis, phagocyte interactions, and biofilm formation.
- To provide insights into the evolution of virulence within the CUG clade.
Main Methods:
- Phenotypic characterization of eight CUG clade species: Candida albicans, C. dubliniensis, C. tropicalis, C. parapsilosis, Clavispora lusitaniae, Meyerozyma guilliermondii, Debaryomyces hansenii, and Lodderomyces elongisporus.
- Assays focused on nutrient utilization, stress tolerance, morphogenesis, interactions with phagocytes, and biofilm formation.
- Comparison of in vitro phenotypes with animal model data and human incidence rates.
Main Results:
- Candida dubliniensis exhibited robust phenotypes, aligning with highly virulent species like C. albicans and C. tropicalis.
- Candida parapsilosis showed lower-than-expected fitness despite its clinical significance.
- In vitro virulence measures were confirmed as useful indicators, providing evolutionary insights.
Conclusions:
- Phenotypic characterization reveals species-specific virulence strategies within the Candida CUG clade.
- The study highlights discrepancies between clinical incidence, animal models, and in vitro virulence assays.
- Findings contribute to understanding the evolutionary dynamics of fungal pathogenicity.
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