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Malassezia pachydermatis Acquires Resistance to Polyenes in the Laboratory Model
Urszula Czyżewska1, Sandra Chmielewska2,3, Marek Bartoszewicz1
1Department of Microbiology and Biotechnology, Faculty of Biology, University of Bialystok, K. Ciolkowskiego 1J, 15-245 Bialystok, Poland.
Abstract:
This study presents a model investigation into the development of tolerance to polyene antifungal drugs (nystatin and natamycin) in strains of Malassezia pachydermatis. This species, commonly associated with external ear canal infections in dogs, has emerged as increasingly significant in the broader context of growing fungal resistance to treatment. In the experiment, 10 strains of M. pachydermatis were passaged over a period of 105 weeks on media containing sublethal concentrations of nystatin and natamycin. Minimal inhibitory (MIC) and minimal fungicidal concentration (MFC) values were regularly assessed to monitor tolerance development. The results revealed a varied response among the strains: Some were eliminated during the process, while others showed a gradual increase in MIC values, up to fivefold in the case of nystatin. In several strains, acquired resistance remained stable even after passaging in drug-free conditions, whereas others reverted to their original susceptibility. The model demonstrated that resistance does not emerge immediately; significant changes appeared only after 30-45 passages. The authors propose this model as a valuable tool for tracking sequential changes that lead to resistance development. Such an approach may support targeted therapy development and help identify strains predisposed to drug adaptation. These findings hold promise for assessing therapeutic risk in immunosuppressed patients and for building resistance datasets that can support artificial intelligence algorithms in predicting fungal resistance mechanisms.
Insights
This study modeled how Malassezia pachydermatis develops tolerance to antifungal drugs like nystatin. Some strains developed stable resistance over time, highlighting the need for better antifungal strategies.
Area of Science:
- Mycology
- Antimicrobial Resistance
Background:
- Malassezia pachydermatis is a yeast species frequently implicated in canine otitis externa.
- Increasing antifungal resistance poses a significant challenge in treating fungal infections.
- Polyene antifungal drugs, such as nystatin and natamycin, are crucial in managing Malassezia infections.
Purpose of the Study:
- To investigate the development of tolerance to nystatin and natamycin in Malassezia pachydermatis.
- To establish a model for observing sequential changes leading to antifungal drug resistance.
- To identify factors influencing drug adaptation in M. pachydermatis strains.
Main Methods:
- Ten strains of M. pachydermatis were subjected to serial passaging over 105 weeks on media with sublethal concentrations of nystatin and natamycin.
- Minimal Inhibitory Concentration (MIC) and Minimal Fungicidal Concentration (MFC) values were regularly determined.
- Drug-free passaging was used to assess the stability of acquired resistance.
Main Results:
- A variable response to drug pressure was observed among M. pachydermatis strains.
- Some strains exhibited a gradual increase in MIC values, up to fivefold for nystatin.
- Acquired resistance was stable in several strains post-drug withdrawal, while others reverted to susceptibility.
- Significant tolerance development was observed after 30-45 passages, not immediately.
Conclusions:
- The developed model effectively tracks sequential changes in antifungal tolerance.
- This model can aid in identifying predisposed strains and assessing therapeutic risks, especially in immunocompromised individuals.
- Findings support the development of targeted therapies and resistance prediction algorithms for fungal infections.
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