Morphology Changes in Human Fungal Pathogens upon Interaction with the Host

Abstract

Morphological changes are a very common and effective strategy for pathogens to survive in the mammalian host. During interactions with their host, human pathogenic fungi undergo an array of morphological changes that are tightly associated with virulence. Candida albicans switches between yeast cells and hyphae during infection. Thermally dimorphic pathogens, such as Histoplasma capsulatum and Blastomyces species transform from hyphal growth to yeast cells in response to host stimuli. Coccidioides and Pneumocystis species produce spherules and cysts, respectively, which allow for the production of offspring in a protected environment. Finally, Cryptococcus species suppress hyphal growth and instead produce an array of yeast cells-from large polyploid titan cells to micro cells. While the morphology changes produced by human fungal pathogens are diverse, they all allow for the pathogens to evade, manipulate, and overcome host immune defenses to cause disease. In this review, we summarize the morphology changes in human fungal pathogens-focusing on morphological features, stimuli, and mechanisms of formation in the host.

Keywords: host-pathogen interaction; human fungal pathogen; hyphae; morphology change; spherules; titan cell.

Figure 1

Evolutionary relationship between common human fungal pathogens that exhibit morphology changes. The tree was generated using Common Tree from the National Center for Biotechnology Information. M. circinelloides belongs to “Fungi incertae sedis”. C. neoformans is in the phylum Basidiomycota. The rest are in the phylum Ascomycota.

Figure 2

Regulation of the dimorphic transition in C. albicans via multiple signaling pathways. Signaling pathways are illustrated in different colors: cyclic AMP (cAMP)- protein kinase A (PKA) pathway (yellow), Hsp90 pathway (green), Rim101 pathway (blue) and Pes1 pathway (purple). Solid lines or arrows represent direct regulation. Dotted lines or arrows represent indirect or unknown regulation. Positive and negative relationships between components are illustrated in black and red, respectively. Transcription factors are illustrated with a rectangle, transcriptional co-repressors with a triangle, and other proteins with an oval.

Figure 3

Regulation of the morphogenetic transition in thermally dimorphic fungal pathogens. (a) H. capsulatum; (b) B. dermatitidis; (c) T. marneffei; (d) P. brasiliensis; and, (e) S. schenckii. Solid lines or arrows represent direct regulation. Dotted lines or arrows represent indirect or unknown regulation. Positive and negative relationships between components are illustrated in black and red, respectively. Transcription factors are illustrated as rectangles, and other proteins as ovals. Proteins controlling hyphal to yeast transitions are indicated in green. Proteins controlling yeast to hyphal transitions are indicated in blue.

Figure 3

Regulation of the morphogenetic transition in thermally dimorphic fungal pathogens. (a) H. capsulatum; (b) B. dermatitidis; (c) T. marneffei; (d) P. brasiliensis; and, (e) S. schenckii. Solid lines or arrows represent direct regulation. Dotted lines or arrows represent indirect or unknown regulation. Positive and negative relationships between components are illustrated in black and red, respectively. Transcription factors are illustrated as rectangles, and other proteins as ovals. Proteins controlling hyphal to yeast transitions are indicated in green. Proteins controlling yeast to hyphal transitions are indicated in blue.

Figure 4

Dimorphic transition of M. circinelloides in response to O₂/CO₂. Positive and negative relationships between components are illustrated in black and red, respectively.

Figure 5

Changes in cell size upon interaction with host. (a) P. jirovecii; (b) C. immitis; and, (c) C. neoformans. Signaling pathways are illustrated with different colors: cAMP-PKA (yellow), Rim101 (blue) and others (green). Solid lines or arrows represent direct regulation. Dotted lines or arrows represent indirect or unknown regulation. Positive and negative relationships between components are illustrated in black and red, respectively. Transcription factors are illustrated as rectangles and other proteins illustrated as ovals.