Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species
Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic <i>Candida</i> species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to s...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/22/2655 |
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| author | Karolina M. Czajka Krishnan Venkataraman Danielle Brabant-Kirwan Stacey A. Santi Chris Verschoor Vasu D. Appanna Ravi Singh Deborah P. Saunders Sujeenthar Tharmalingam |
| author_facet | Karolina M. Czajka Krishnan Venkataraman Danielle Brabant-Kirwan Stacey A. Santi Chris Verschoor Vasu D. Appanna Ravi Singh Deborah P. Saunders Sujeenthar Tharmalingam |
| author_sort | Karolina M. Czajka |
| collection | DOAJ |
| description | Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic <i>Candida</i> species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in <i>Candida</i> species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: <i>tac1</i> and <i>mrr1</i>; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent <i>Candida</i> species. Notably, <i>N. glabrata</i>, <i>P. kudriavzevii</i> and <i>C. auris</i> demonstrate fluconazole resistance. |
| first_indexed | 2024-03-09T16:55:40Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:55:40Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-52a8513d905e414c8b53a35b79c488fe2023-11-24T14:35:30ZengMDPI AGCells2073-44092023-11-011222265510.3390/cells12222655Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> SpeciesKarolina M. Czajka0Krishnan Venkataraman1Danielle Brabant-Kirwan2Stacey A. Santi3Chris Verschoor4Vasu D. Appanna5Ravi Singh6Deborah P. Saunders7Sujeenthar Tharmalingam8Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaMedical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaHealth Sciences North Research Institute, Sudbury, ON P3E 2H2, CanadaHealth Sciences North Research Institute, Sudbury, ON P3E 2H2, CanadaMedical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaSchool of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, CanadaMedical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaMedical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaMedical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, CanadaCandidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic <i>Candida</i> species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in <i>Candida</i> species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: <i>tac1</i> and <i>mrr1</i>; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent <i>Candida</i> species. Notably, <i>N. glabrata</i>, <i>P. kudriavzevii</i> and <i>C. auris</i> demonstrate fluconazole resistance.https://www.mdpi.com/2073-4409/12/22/2655antifungalresistance<i>Candida</i>azolespolyenesechinocandins |
| spellingShingle | Karolina M. Czajka Krishnan Venkataraman Danielle Brabant-Kirwan Stacey A. Santi Chris Verschoor Vasu D. Appanna Ravi Singh Deborah P. Saunders Sujeenthar Tharmalingam Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species Cells antifungal resistance <i>Candida</i> azoles polyenes echinocandins |
| title | Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species |
| title_full | Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species |
| title_fullStr | Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species |
| title_full_unstemmed | Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species |
| title_short | Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic <i>Candida</i> Species |
| title_sort | molecular mechanisms associated with antifungal resistance in pathogenic i candida i species |
| topic | antifungal resistance <i>Candida</i> azoles polyenes echinocandins |
| url | https://www.mdpi.com/2073-4409/12/22/2655 |
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