The Role of Secretory Pathways in  Candida albicans  Pathogenesis

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Abstract

Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

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Most cited references 332

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SNAREs--engines for membrane fusion.

Reinhard Jahn, Richard H. Scheller (2006)

Since the discovery of SNARE proteins in the late 1980s, SNAREs have been recognized as key components of protein complexes that drive membrane fusion. Despite considerable sequence divergence among SNARE proteins, their mechanism seems to be conserved and is adaptable for fusion reactions as diverse as those involved in cell growth, membrane repair, cytokinesis and synaptic transmission. A fascinating picture of these robust nanomachines is emerging.

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The mechanisms of vesicle budding and fusion.

Juan Bonifacino, Benjamin Glick (2004)

Genetic and biochemical analyses of the secretory pathway have produced a detailed picture of the molecular mechanisms involved in selective cargo transport between organelles. This transport occurs by means of vesicular intermediates that bud from a donor compartment and fuse with an acceptor compartment. Vesicle budding and cargo selection are mediated by protein coats, while vesicle targeting and fusion depend on a machinery that includes the SNARE proteins. Precise regulation of these two aspects of vesicular transport ensures efficient cargo transfer while preserving organelle identity.

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Cellular internalization of exosomes occurs through phagocytosis.

Du Feng, Wen-Long Zhao, Yun-Ying Ye … (2010)

Exosomes play important roles in many physiological and pathological processes. However, the exosome-cell interaction mode and the intracellular trafficking pathway of exosomes in their recipient cells remain unclear. Here, we report that exosomes derived from K562 or MT4 cells are internalized more efficiently by phagocytes than by non-phagocytic cells. Most exosomes were observed attached to the plasma membrane of non-phagocytic cells, while in phagocytic cells these exosomes were found to enter via phagocytosis. Specifically, they moved to phagosomes together with phagocytic polystyrene carboxylate-modified latex beads (biospheres) and were further sorted into phagolysosomes. Moreover, exosome internalization was dependent on the actin cytoskeleton and phosphatidylinositol 3-kinase, and could be inhibited by the knockdown of dynamin2 or overexpression of a dominant-negative form of dynamin2. Further, antibody pretreatment assays demonstrated that tim4 but not tim1 was involved in exosomes uptake. We also found that exosomes did not enter the internalization pathway involving caveolae, macropinocytosis and clathrin-coated vesicles. Our observation that the cellular uptake of exosomes occurs through phagocytosis has important implications for exosome-cell interactions and the exosome intracellular trafficking pathway.

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Author and article information

Journal

Journal ID (nlm-ta): J Fungi (Basel)

Journal ID (iso-abbrev): J Fungi (Basel)

Journal ID (publisher-id): jof

Title: Journal of Fungi

Publisher: MDPI

ISSN (Electronic): 2309-608X

Publication date (Electronic): 24 February 2020

Publication date Collection: March 2020

Volume: 6

Issue: 1

Electronic Location Identifier: 26

Affiliations

[1 ]Medicine Service, White River Junction VA Medical Center, White River Junction, VT 05009, USA; Christiane.Rollenhagen@ 123456dartmouth.edu (C.R.); sahil.mamtani@ 123456gmail.com (S.M.); Dakota.C.Ma.22@ 123456dartmouth.edu (D.M.); Reva.Dixit.22@ 123456dartmouth.edu (R.D.); Susan.K.Eszterhas@ 123456dartmouth.edu (S.E.)

[2 ]Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA

[3 ]Dartmouth College, Hanover, NH 03755, USA

Author notes

[* ]Correspondence: samuel.a.lee@ 123456dartmouth.edu

[†]

These authors contributed equally to this work.

Article

Publisher ID: jof-06-00026

DOI: 10.3390/jof6010026

PMC ID: 7151058

PubMed ID: 32102426

SO-VID: da5158b5-5182-48e4-8e40-a526c887b2e5

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

The Role of Secretory Pathways in Candida albicans Pathogenesis

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Abstract

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Bacterial vaginosis and biofilm

Most cited references 332

SNAREs--engines for membrane fusion.

The mechanisms of vesicle budding and fusion.

Cellular internalization of exosomes occurs through phagocytosis.

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