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Title (en)
Proline catabolism is a key factor facilitating Candida albicans pathogenicity
Language
English
Description (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.
Keywords (en)
Saccharomyces-Cerevisiae; Amino-Acids; Mitochondrial Respiration; Metabolism; Infections; Mutant; Viability; Transport; Virulence; Activator
DOI
10.1371/journal.ppat.1011677
Author of the digital object
Fitz Gerald S. Silao  (Stockholm University)
Per O. Ljungdahl  (Peuckert)
Christiane Peuckert  (Peuckert)
Changbin Chen  (Chinese Academy of Sciences)
Karl Kuchler  (Medical University of Vienna)
Steffen Rupp  (Fraunhofer Institute for Interfacial Engineering and Biotechnology)
Constantin F Urban  (Umeå University)
Thomas Lion  (St. Anna Kinderkrebsforschung e.V.)
Meliza Ward  (Stockholm University)
Filomena Nogueira  (Medical University of Vienna / St. Anna Kinderkrebsforschung e.V.)
Sabrina Jenull  (University of Veterinary Medicine Vienna / Medical University of Vienna)
Nathalie Uwamohoro  (Umeå University)
Kicki Ryman  (Stockholm University)
Andreas Kühbacher  (Fraunhofer Institute for Interfacial Engineering and Biotechnology)
Tong Jiang  (Chinese Academy of Sciences)
Biborka Bereczky-Veress  (Stockholm University)
Format
application/pdf
Size
4.2 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
PloS Pathogens
Pages or Volume
42
Volume
19
Number
11
Publisher
Public Library of Science
Publication Date
2023