Proline catabolism is key to facilitating Candida albicans pathogenicity

Silao, F. G. S.; Jiang, T.; Bereczky-Veress, B.; Kuehbacher, A.; Ryman, K.; Uwamohoro, N.; Jenull, S.; Nogueira, F.; Ward, M.; Lion, T.; Urban, C. F.; Rupp, S.; Kuchler, K.; Chen, C.; Peuckert, C.; Ljungdahl, P. O.

doi:10.1101/2023.01.17.524449

bioRxiv · 10.1101/2023.01.17.524449

Proline catabolism is key to facilitating Candida albicans pathogenicity

Silao, F. G. S.·Jiang, T.·Bereczky-Veress, B.·Kuehbacher, A.·Ryman, K.·Uwamohoro, N.·Jenull, S.·Nogueira, F.·Ward, M.·Lion, T.·Urban, C. F.·Rupp, S.·Kuchler, K.·Chen, C.·Peuckert, C.·Ljungdahl, P. O.

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Abstract

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 P5C, which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells colonizing 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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Silao, F. G. S., Jiang, T., Bereczky-Veress, B., Kuehbacher, A., Ryman, K., Uwamohoro, N., Jenull, S., Nogueira, F., Ward, M., Lion, T., Urban, C. F., Rupp, S., Kuchler, K., Chen, C., Peuckert, C., Ljungdahl, P. O.. 2023-01-18. Proline catabolism is key to facilitating Candida albicans pathogenicity. https://doi.org/10.1101/2023.01.17.524449

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