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Proline catabolism is a key factor facilitating Candida albicans pathogenicity

Silao, Fitz-Gerald S., 1985- (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
Jiang, Tong (author)
Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China
Bereczky-Veress, Biborka (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Kühbacher, Andreas (author)
Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany
Ryman, Kicki (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
Uwamahoro, Nathalie (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi
Jenull, Sabrina (author)
Medical University of Vienna, Max F. Perutz Laboratories GmbH, Department of Medical Biochemistry, Vienna, Austria; Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria
Nogueira, Filomena (author)
Medical University of Vienna, Max F. Perutz Laboratories GmbH, Department of Medical Biochemistry, Vienna, Austria; St. Anna Kinderkrebsforschung e.V., Children’s Cancer Research Institute, Vienna, Austria
Ward, Meliza (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
Lion, Thomas (author)
St. Anna Kinderkrebsforschung e.V., Children’s Cancer Research Institute, Vienna, Austria
Urban, Constantin F. (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi
Rupp, Steffen (author)
Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany
Kuchler, Karl (author)
Medical University of Vienna, Max F. Perutz Laboratories GmbH, Department of Medical Biochemistry, Vienna, Austria
Chen, Changbin (author)
Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China
Peuckert, Christiane (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
Ljungdahl, Per O. (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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 (creator_code:org_t)
Public Library of Science (PLoS), 2023
2023
English.
In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:11 NOVEMBER
Related links:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

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