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Reduced virulence of Candida albicans mutants affected in multidrug resistance
J M Becker1, L K Henry, W Jiang
1Department of Microbiology, University of Tennessee, Knoxville 37996-0845, USA.
Abstract:
Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.
Insights
Disrupting the multidrug resistance gene in Candida albicans increased kidney colonization but reduced virulence. This suggests fungal efflux pumps are key to pathogenicity.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Candida albicans is an opportunistic fungal pathogen.
- Multidrug resistance (MDR) mechanisms in fungi are not fully understood.
- Efflux pumps are implicated in MDR in various organisms.
Purpose of the Study:
- To investigate the role of the Candida albicans multidrug resistance gene (CaMDR1) in fungal pathogenicity.
- To determine the impact of CaMDR1 disruption on fungal colonization and virulence.
Main Methods:
- Generation of CaMDR1-disrupted (mdr-) mutant strains of Candida albicans.
- Infection of a mouse model with wild-type (MDR+) and mdr- strains.
- Assessment of fungal colonization in mouse kidneys.
- Evaluation of fungal virulence and related properties.
Main Results:
- CaMDR1 disruption led to significantly increased colonization of mouse kidneys by Candida albicans.
- Mutant strains exhibited markedly reduced virulence despite high colonization levels.
- No significant differences in colonization or dissemination properties were observed between MDR+ and mdr- strains.
Conclusions:
- Specific fungal efflux pumps, like CaMDR1, play a critical role in Candida albicans pathogenicity.
- Efflux pump activity may be dissociated from fungal colonization and dissemination capabilities.
- Targeting efflux pumps could be a strategy to combat Candida albicans infections.