Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure
Abstract
:1. Introduction
2. Materials and Methods
2.1. Strains, Media and Growth Conditions
2.2. Broth Microdilution Assay to Determine Minimum Inhibitory Concentration (MIC)
2.3. In Vitro Evolution of Strains
2.4. Sequencing of FKS1 Hot Spots HS1 and HS2 Regions
3. Results and Discussion
3.1. Caspofungin-Adapted Parental Mutants Have Decreased Susceptibility to Caspofungin Only
3.2. Generation and Properties of Strains That Evolved from Caspofungin-Adapted Mutants
3.3. Medical Importance
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Strain | CAS | MFG ** | ANI ** |
---|---|---|---|
No ploidy change | |||
Parent JRCT1 JMC200-2-5 JMC160-2-5 | − + + | − + + | − + + |
Ch5 monosomic | |||
Parent SC5314 SMC60-3-4 SMC60-2-5 | − + + | − − − − − | − − − − − |
Iso-Ch5R | |||
Parent JRCT1 JMC120-1-6 JMC120-2-5 | − + + | − − − − − | − INC INC |
D | CAS | MFG | ANI | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
CAS-Adapted Parental Mutant * | 2X MIC Conc. (µg/mL) | No. of Recove-red Cols. | No. of Evolved Colonies—Increase of MICs | No. of Colonies W. 16- or 32-Fold Increase of MICs | % of Colonies w. 16- or 32-Fold Increase of MICs | No. of Evolved Colonies—Increase of MICs | No. of Colonies W. 16- or 32-Fold Increase of MICs | % of Colonies W. 16- or 32-Fold Increase of MICs | No. of Evolved Colonies—Increase of MICs | No. of Colonies W. 16- or 32-Fold Increase of MICs | % of Colonies W. 16- or 32-Fold Increase of MICs ** |
JMC200-2-5 No ploidy change | 0.500 | 26 | 3–4-fold 1–8-fold | 0 | NA | 1–2-fold | 0 | NA | 1–2-fold | 0 | NA |
JMC160-2-5 No ploidy change | 0.500 | 26 | 4–2-fold 5–4-fold 2–8-fold 1–128-fold | 1 | 3.8% | 0 | 0 | NA | 0 | 0 | NA |
JMC120-2-5 iso-Ch5 | 0.125 | 5 | 3–8-fold | 0 | NA | 2–32-fold 1–128-fold | 3 | 60% | 2–16-fold 1–64-fold | 3 | 60% |
JMC120-1-6 iso-Ch5R | 0.125 | 17 | 2–4-fold 2–8-fold 1–16-fold 3–32-fold 2–64-fold | 6 | 35% | 2–4-fold, 1–8-fold 1–16-fold 5–64-fold | 6 | 35% | 1–4-fold, 2–8-fold 3–16-fold 2–32-fold 1-64-fold | 6 | 35% |
SMC60-3-4 Ch5 mono | 0.250 | 12 | 2–2-fold 3–16-fold 4–32-fold 2–64-fold | 9 | 75% | 1–4-fold 1–8-fold 4–16-fold 1–32-fold 1–64-fold 1–128-fold | 7 | 58.3% | 1–8-fold 3–16-fold 1–64-fold 3–128-fold 1–256-fold | 8 | 66.7% |
SMC60-2-5 Ch5 mono | 0.250 | 20 | 2–2-fold 2–4-fold 1–8-fold 2–16-fold 3–32-fold | 5 | 25% | 1–8-fold 3–16-fold 1–32-fold 2–64-fold 2–128-fold | 8 | 40% | 2–4-fold 1–8-fold 1–32-fold 2–128-fold 3–256-fold | 6 | 30% |
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Husain, F.; Yadav, A.; Sah, S.K.; Hayes, J.J.; Rustchenko, E. Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure. Microorganisms 2023, 11, 23. https://doi.org/10.3390/microorganisms11010023
Husain F, Yadav A, Sah SK, Hayes JJ, Rustchenko E. Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure. Microorganisms. 2023; 11(1):23. https://doi.org/10.3390/microorganisms11010023
Chicago/Turabian StyleHusain, Farha, Anshuman Yadav, Sudisht K. Sah, Jeffrey J. Hayes, and Elena Rustchenko. 2023. "Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure" Microorganisms 11, no. 1: 23. https://doi.org/10.3390/microorganisms11010023
APA StyleHusain, F., Yadav, A., Sah, S. K., Hayes, J. J., & Rustchenko, E. (2023). Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure. Microorganisms, 11(1), 23. https://doi.org/10.3390/microorganisms11010023