<i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure
<i>Candida albicans</i> is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of <i>FKS1</i> resistance mutati...
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MDPI AG
2022-12-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/1/23 |
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| author | Farha Husain Anshuman Yadav Sudisht K. Sah Jeffrey J. Hayes Elena Rustchenko |
| author_facet | Farha Husain Anshuman Yadav Sudisht K. Sah Jeffrey J. Hayes Elena Rustchenko |
| author_sort | Farha Husain |
| collection | DOAJ |
| description | <i>Candida albicans</i> is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of <i>FKS1</i> resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs. |
| first_indexed | 2024-03-09T11:38:51Z |
| format | Article |
| id | doaj.art-1137d420806449168ad9ec9a88a819b0 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T11:38:51Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-1137d420806449168ad9ec9a88a819b02023-11-30T23:35:18ZengMDPI AGMicroorganisms2076-26072022-12-011112310.3390/microorganisms11010023<i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug PressureFarha Husain0Anshuman Yadav1Sudisht K. Sah2Jeffrey J. Hayes3Elena Rustchenko4Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA<i>Candida albicans</i> is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of <i>FKS1</i> resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs.https://www.mdpi.com/2076-2607/11/1/23<i>Candida albicans</i>caspofunginechinocandinscross-adaptationevolution of drug toleranceaneuploidy |
| spellingShingle | Farha Husain Anshuman Yadav Sudisht K. Sah Jeffrey J. Hayes Elena Rustchenko <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure Microorganisms <i>Candida albicans</i> caspofungin echinocandins cross-adaptation evolution of drug tolerance aneuploidy |
| title | <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure |
| title_full | <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure |
| title_fullStr | <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure |
| title_full_unstemmed | <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure |
| title_short | <i>Candida albicans</i> Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure |
| title_sort | i candida albicans i strains adapted to caspofungin due to aneuploidy become highly tolerant under continued drug pressure |
| topic | <i>Candida albicans</i> caspofungin echinocandins cross-adaptation evolution of drug tolerance aneuploidy |
| url | https://www.mdpi.com/2076-2607/11/1/23 |
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