The regulation of hyphae growth in Candida albicans

Abstract

In the last decades, Candida albicans has served as the leading causal agent of life-threatening invasive infections with mortality rates approaching 40% despite treatment. Candida albicans (C. albicans) exists in three biological phases: yeast, pseudohyphae, and hyphae. Hyphae, which represent an important phase in the disease process, can cause tissue damage by invading mucosal epithelial cells then leading to blood infection. In this review, we summarized recent results from different fields of fungal cell biology that are instrumental in understanding hyphal growth. This includes research on the differences among C. albicans phases; the regulatory mechanism of hyphal growth, extension, and maintaining cutting-edge polarity; cross regulations of hyphal development and the virulence factors that cause serious infection. With a better understanding of the mechanism on mycelium formation, this review provides a theoretical basis for the identification of targets in candidiasis treatment. It also gives some reference to the study of antifungal drugs.

Keywords: Candida albicans; Oral candidiasis; fungi; hyphae; mycelium.

Figure 1.

Schematic diagram of yeast, pseudohypha, and hypha (black arrow indicates septin ring).

Figure 2.

Cek MAPK pathway. The Cek1 mitogen-activated protein kinase pathway (MAPK pathway, dark blue) is induced by the embedded matrix environment (light blue), cell wall damage (dark blue), and low nitrogen (gray) and eventually leads to mycelium formation via the phosphorylation of transcription factor Cph1, Ace2.

Figure 3.

Regulatory models of cAMP-PKA signaling pathway in C. albicans.

Figure 4.

The Rim101‑pH sensing pathway.

Figure 5.

Hog MAPK pathway.

Figure 6.

Tup1-mediated negative regulatory pathway.

Figure 7.

Key factors of mycelial elongation. Transcription factors such as Efg1 and Cph1 are involved in this regulation process. Eed1, Hgc1, Ume6 play key roles in mycelial elongation. Ume6 and Eed1 also negatively regulate Tup1 and Nrg1.

Figure 8.

Transport secretory vesicles to mycelium tip. The secretory vesicles are transported to the top by actin. All vesicles will carry Sec4. After forming Spitzenkörper, the vesicles are polarized by the polar bodies and transported to the cell surface by a motorized protein strip.

Figure 9.

The pathway of hyphal formation. Different colored circles indicate different signaling pathways. The gray rectangles represent transcription factors. “?” represents that the mechanism is still uncleared here.