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Proline catabolism is a key factor facilitating Candida albicans pathogenicity
Department of Molecular Biosciences, The Wenner-Gren Institute, Science for Life Laboratory, Stockholm University, Solna, Sweden.
Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
Intravital Microscopy Facility, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany.
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2023 (Engelska)Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 19, nr 11 NOVEMBER, artikel-id e1011677Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

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Public Library of Science (PLoS), 2023. Vol. 19, nr 11 NOVEMBER, artikel-id e1011677
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Mikrobiologi inom det medicinska området Mikrobiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-216679DOI: 10.1371/journal.ppat.1011677Scopus ID: 2-s2.0-85175854519OAI: oai:DiVA.org:umu-216679DiVA, id: diva2:1812513
Tillgänglig från: 2023-11-16 Skapad: 2023-11-16 Senast uppdaterad: 2023-11-16Bibliografiskt granskad

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Uwamahoro, NathalieUrban, Constantin F.

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Uwamahoro, NathalieUrban, Constantin F.
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Umeå Centre for Microbial Research (UCMR)Institutionen för klinisk mikrobiologi
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