Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response
Opportunistic pathogen <i>Candida albicans</i> possesses multiple virulence factors which enable colonization and infection of host tissues. <i>Candida</i>-related infections frequently occur in immunocompromised patients, which is related to an insufficient inflammatory resp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3966 |
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| author | Daria Derkacz Anna Krasowska |
| author_facet | Daria Derkacz Anna Krasowska |
| author_sort | Daria Derkacz |
| collection | DOAJ |
| description | Opportunistic pathogen <i>Candida albicans</i> possesses multiple virulence factors which enable colonization and infection of host tissues. <i>Candida</i>-related infections frequently occur in immunocompromised patients, which is related to an insufficient inflammatory response. Furthermore, immunosuppression and multidrug resistance of <i>C. albicans</i> clinical isolates make the treatment of candidiasis a challenge for modern medicine. The most common resistance mechanism of <i>C. albicans</i> to antifungals includes point mutations in the <i>ERG11</i> gene, which encodes target protein for azoles. We investigated whether the mutations or deletion of the <i>ERG11</i> gene influence the pathogen-host interactions. We prove that both <i>C. albicans erg11∆/∆</i> and <i>ERG11K143R/K143R</i> exhibit increased cell surface hydrophobicity. Additionally, <i>C. albicans</i> KS058 has an impaired ability of biofilm and hyphae formation. Analysis of the inflammatory response of human dermal fibroblasts and vaginal epithelial cell lines revealed that altered morphology of <i>C. albicans erg11∆/∆</i> results in a significantly weaker immune response. <i>C. albicans ERG11K143R/K143R</i> triggered stronger production of pro-inflammatory response. Analysis of genes encoding adhesins confirmed differences in the expression pattern of key adhesins for both <i>erg11∆/∆</i> and <i>ERG11K143R/K143R</i> strains. Obtained data indicate that alterations in Erg11p consequence in resistance to azoles and affect the key virulence factors and inflammatory response of host cells. |
| first_indexed | 2024-03-11T08:41:47Z |
| format | Article |
| id | doaj.art-5490f9eae71c468cb9c67208603ebec7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:41:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5490f9eae71c468cb9c67208603ebec72023-11-16T21:07:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244396610.3390/ijms24043966Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory ResponseDaria Derkacz0Anna Krasowska1Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, PolandFaculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, PolandOpportunistic pathogen <i>Candida albicans</i> possesses multiple virulence factors which enable colonization and infection of host tissues. <i>Candida</i>-related infections frequently occur in immunocompromised patients, which is related to an insufficient inflammatory response. Furthermore, immunosuppression and multidrug resistance of <i>C. albicans</i> clinical isolates make the treatment of candidiasis a challenge for modern medicine. The most common resistance mechanism of <i>C. albicans</i> to antifungals includes point mutations in the <i>ERG11</i> gene, which encodes target protein for azoles. We investigated whether the mutations or deletion of the <i>ERG11</i> gene influence the pathogen-host interactions. We prove that both <i>C. albicans erg11∆/∆</i> and <i>ERG11K143R/K143R</i> exhibit increased cell surface hydrophobicity. Additionally, <i>C. albicans</i> KS058 has an impaired ability of biofilm and hyphae formation. Analysis of the inflammatory response of human dermal fibroblasts and vaginal epithelial cell lines revealed that altered morphology of <i>C. albicans erg11∆/∆</i> results in a significantly weaker immune response. <i>C. albicans ERG11K143R/K143R</i> triggered stronger production of pro-inflammatory response. Analysis of genes encoding adhesins confirmed differences in the expression pattern of key adhesins for both <i>erg11∆/∆</i> and <i>ERG11K143R/K143R</i> strains. Obtained data indicate that alterations in Erg11p consequence in resistance to azoles and affect the key virulence factors and inflammatory response of host cells.https://www.mdpi.com/1422-0067/24/4/3966<i>Candida albicans</i>Erg11pbiofilmfilamentationadhesinsinflammatory response |
| spellingShingle | Daria Derkacz Anna Krasowska Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response International Journal of Molecular Sciences <i>Candida albicans</i> Erg11p biofilm filamentation adhesins inflammatory response |
| title | Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response |
| title_full | Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response |
| title_fullStr | Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response |
| title_full_unstemmed | Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response |
| title_short | Alterations in the Level of Ergosterol in <i>Candida albicans</i>’ Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response |
| title_sort | alterations in the level of ergosterol in i candida albicans i plasma membrane correspond with changes in virulence and result in triggering diversed inflammatory response |
| topic | <i>Candida albicans</i> Erg11p biofilm filamentation adhesins inflammatory response |
| url | https://www.mdpi.com/1422-0067/24/4/3966 |
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