<i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins
The opportunistic fungus <i>Candida albicans</i> is the leading cause of invasive candidiasis in immune-compromised individuals. Drugs from the echinocandin (ECN) class, including caspofungin, are used as a first line of therapy against invasive candidiasis. The only known mechanism of c...
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MDPI AG
2024-03-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/10/3/224 |
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| author | Anshuman Yadav Sudisht K. Sah David S. Perlin Elena Rustchenko |
| author_facet | Anshuman Yadav Sudisht K. Sah David S. Perlin Elena Rustchenko |
| author_sort | Anshuman Yadav |
| collection | DOAJ |
| description | The opportunistic fungus <i>Candida albicans</i> is the leading cause of invasive candidiasis in immune-compromised individuals. Drugs from the echinocandin (ECN) class, including caspofungin, are used as a first line of therapy against invasive candidiasis. The only known mechanism of clinical resistance to ECNs is point mutations in the <i>FKS1</i> gene, which encodes the drug target. However, many clinical isolates developed decreased ECN susceptibilities in the absence of resistance-associated <i>FKS1</i> mutations. We have identified 15 <i>C. albicans</i> genes that contribute to decreased drug susceptibility. We explored the expression of these 15 genes in clinical isolates with different levels of ECN susceptibility. We found that these 15 genes are expressed in clinical isolates with or without <i>FKS1</i> mutations, including those strains that are less susceptible to ECNs. In addition, <i>FKS1</i> expression was increased in such less susceptible isolates compared to highly susceptible isolates. Similarities of gene expression patterns between isolates with decreased ECN susceptibilities in the absence of <i>FKS1</i> mutations and clinically resistant isolates with mutations in <i>FKS1</i> suggest that clinical isolates with decreased ECN susceptibilities may be a precursor to development of resistance. |
| first_indexed | 2024-04-24T18:07:18Z |
| format | Article |
| id | doaj.art-ad5a11666a2747199ebfea4351b99f55 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-04-24T18:07:18Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-ad5a11666a2747199ebfea4351b99f552024-03-27T13:49:45ZengMDPI AGJournal of Fungi2309-608X2024-03-0110322410.3390/jof10030224<i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to EchinocandinsAnshuman Yadav0Sudisht K. Sah1David S. Perlin2Elena Rustchenko3Department 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, USAHackensack Meridian School of Medicine, Center for Discovery and Innovation, Nutley, NJ 07110, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USAThe opportunistic fungus <i>Candida albicans</i> is the leading cause of invasive candidiasis in immune-compromised individuals. Drugs from the echinocandin (ECN) class, including caspofungin, are used as a first line of therapy against invasive candidiasis. The only known mechanism of clinical resistance to ECNs is point mutations in the <i>FKS1</i> gene, which encodes the drug target. However, many clinical isolates developed decreased ECN susceptibilities in the absence of resistance-associated <i>FKS1</i> mutations. We have identified 15 <i>C. albicans</i> genes that contribute to decreased drug susceptibility. We explored the expression of these 15 genes in clinical isolates with different levels of ECN susceptibility. We found that these 15 genes are expressed in clinical isolates with or without <i>FKS1</i> mutations, including those strains that are less susceptible to ECNs. In addition, <i>FKS1</i> expression was increased in such less susceptible isolates compared to highly susceptible isolates. Similarities of gene expression patterns between isolates with decreased ECN susceptibilities in the absence of <i>FKS1</i> mutations and clinically resistant isolates with mutations in <i>FKS1</i> suggest that clinical isolates with decreased ECN susceptibilities may be a precursor to development of resistance.https://www.mdpi.com/2309-608X/10/3/224<i>Candida albicans</i>echinocandin susceptibilitydrug adaptationclinical isolates |
| spellingShingle | Anshuman Yadav Sudisht K. Sah David S. Perlin Elena Rustchenko <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins Journal of Fungi <i>Candida albicans</i> echinocandin susceptibility drug adaptation clinical isolates |
| title | <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins |
| title_full | <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins |
| title_fullStr | <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins |
| title_full_unstemmed | <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins |
| title_short | <i>Candida albicans</i> Genes Modulating Echinocandin Susceptibility of Caspofungin-Adapted Mutants Are Constitutively Expressed in Clinical Isolates with Intermediate or Full Resistance to Echinocandins |
| title_sort | i candida albicans i genes modulating echinocandin susceptibility of caspofungin adapted mutants are constitutively expressed in clinical isolates with intermediate or full resistance to echinocandins |
| topic | <i>Candida albicans</i> echinocandin susceptibility drug adaptation clinical isolates |
| url | https://www.mdpi.com/2309-608X/10/3/224 |
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