Vacuolar trafficking and Candida albicans pathogenesis

Abstract

The vacuole is likely to play a variety of roles in supporting host colonization and infection by pathogenic species of fungi. In the human pathogen Candida albicans, the vacuole undergoes dynamic morphological shifts during the production of the tissue invasive hyphal form, and this organelle is required for virulence. Recent efforts in my lab have focused on defining which vacuolar trafficking pathways are required for C. albicans hyphal growth and pathogenesis. Our results indicate that there are several distinct trafficking routes between the Golgi apparatus and vacuole. However, there is a large degree of functional overlap between each with respect to their roles in hyphal growth and virulence. Herein we consider these results and propose that during hyphal growth, specific trafficking routes maybe less important than the aggregate vacuolar trafficking capacity. 

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Figures and Tables

Figure 1 Proposed roles for the fungal vacuole in Candida albicans pathogenesis.

Figure 2 Vacuolar trafficking and regulation in Candida albicans. Our results have established that both the Aps3p (AP-3) and Vps21p (endosomal) dependent vacuolar trafficking routes contribute to hyphal growth, presumably by facilitating the vacuolation of sub-apical cells. Our data also suggest a second Golgi→endosome→vacuole trafficking route exists (dashed line), facilitated by a GTPase closely related to Vps21p. While loss of either pathway alone results in minor defects in hyphal growth, loss of more than one seems to lead to severe defects. However, our results have not demonstrated a role for autophagy in C. albicans hyphal growth or virulence (dotted line).17 We suggest that activation of a hyphal specific transcriptional program through the Ume6p transcription factor, stimulates vacuolar trafficking through AP-3 and endosomal pathways to facilitate sub-apical vacuolation.

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