Proline catabolism is a key factor facilitating Candida albicans pathogenicity.
Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline s...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011677&type=printable |
| _version_ | 1827376852377796608 |
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| author | Fitz Gerald S Silao Tong Jiang Biborka Bereczky-Veress Andreas Kühbacher Kicki Ryman Nathalie Uwamohoro Sabrina Jenull Filomena Nogueira Meliza Ward Thomas Lion Constantin F Urban Steffen Rupp Karl Kuchler Changbin Chen Christiane Peuckert Per O Ljungdahl |
| author_facet | Fitz Gerald S Silao Tong Jiang Biborka Bereczky-Veress Andreas Kühbacher Kicki Ryman Nathalie Uwamohoro Sabrina Jenull Filomena Nogueira Meliza Ward Thomas Lion Constantin F Urban Steffen Rupp Karl Kuchler Changbin Chen Christiane Peuckert Per O Ljungdahl |
| author_sort | Fitz Gerald S Silao |
| collection | DOAJ |
| description | Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells infecting a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not of put2-/- cells. Multiple members of the Candida species complex, including C. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens. |
| first_indexed | 2024-03-08T12:28:55Z |
| format | Article |
| id | doaj.art-0b59d9f2213840038a947b753fb88067 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-08T12:28:55Z |
| publishDate | 2023-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0b59d9f2213840038a947b753fb880672024-01-22T05:30:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-11-011911e101167710.1371/journal.ppat.1011677Proline catabolism is a key factor facilitating Candida albicans pathogenicity.Fitz Gerald S SilaoTong JiangBiborka Bereczky-VeressAndreas KühbacherKicki RymanNathalie UwamohoroSabrina JenullFilomena NogueiraMeliza WardThomas LionConstantin F UrbanSteffen RuppKarl KuchlerChangbin ChenChristiane PeuckertPer O LjungdahlCandida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells infecting a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not of put2-/- cells. Multiple members of the Candida species complex, including C. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011677&type=printable |
| spellingShingle | Fitz Gerald S Silao Tong Jiang Biborka Bereczky-Veress Andreas Kühbacher Kicki Ryman Nathalie Uwamohoro Sabrina Jenull Filomena Nogueira Meliza Ward Thomas Lion Constantin F Urban Steffen Rupp Karl Kuchler Changbin Chen Christiane Peuckert Per O Ljungdahl Proline catabolism is a key factor facilitating Candida albicans pathogenicity. PLoS Pathogens |
| title | Proline catabolism is a key factor facilitating Candida albicans pathogenicity. |
| title_full | Proline catabolism is a key factor facilitating Candida albicans pathogenicity. |
| title_fullStr | Proline catabolism is a key factor facilitating Candida albicans pathogenicity. |
| title_full_unstemmed | Proline catabolism is a key factor facilitating Candida albicans pathogenicity. |
| title_short | Proline catabolism is a key factor facilitating Candida albicans pathogenicity. |
| title_sort | proline catabolism is a key factor facilitating candida albicans pathogenicity |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011677&type=printable |
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