Review Article

Hyphal Growth in Human Fungal Pathogens and Its Role in Virulence

Figure 2

Models and examples of hyphal invasion in vivo. (a) Biofilms form on mucosal and abiotic surfaces by initial adhesion of yeast cells, followed by hypha germination and the deposition of extracellular matrix polysaccharides (blue). On mucosa or soft silicones, hyphae penetrate the underlying layers. (i) Rat denture biofilm formation after 48 h [37]. (ii) Hyphae penetrate the silicone of a voice prosthesis, causing it to expand and stiffen [7]. (iii) In silico construction of a biofilm showing the thick hyphal matrix (green) and leading edge of β-glucan deposition at the hyphal tips (red) [38]. (b) Induced uptake of yeast and newly germinating hyphae by epithelial cells or phagocytosis by macrophages is followed by sustained polarised growth, which breaches the host cell plasma membrane and permits the escape of the fungus. (i) C. albicans hyphae are engulfed by epithelial cells during induced uptake [39]. (ii) C. albicans avoids being killed by a macrophage by undergoing morphogenesis and breaching the macrophage membrane [40]. (c) Active penetration of endothelial cells and reversion to yeast growth in the tissue below. (i) Biopsy of murine lung with invasive aspergillosis, showing septate hyphae stained with blancophor [41]. (ii) Histological section of murine kidney showing C. albicans lesion containing yeast, hyphae, and infiltrate of neutrophils (courtesy D. MacCallum). (iii) Galvanotropism: C. albicans wild-type hyphae orient towards the cathode when grown in an applied electric field (10 V/cm) [42]. (iv) All tropic responses were abolished in the rsr1Δ mutant, which was attenuated in virulence. Cell polarity was maintained, but hyphal tip directionality was erratic [42].