Box 2 | Fungal infections: morphogenesis and virulence

From the following article:

Immunity to fungal infections

Luigina Romani

Nature Reviews Immunology 4, 11-24 (January 2004)

doi:10.1038/nri1255

Humans are constantly exposed to fungi, but only a limited number of fungi cause severe infections. So, pathogenicity is not a stable characteristic of most fungi. The pathogenesis of fungal infections involves several virulence factors that allow fungal survival and persistence in the host, eventually leading to tissue damage. Some virulence factors are of obvious importance, such as: various complementary structures through which fungi adhere to host tissues and the extracellular matrix; the production of phospholipases, proteases and elastases that cause tissue damage and impairment of host defences; the ability to switch to metabolic pathways that are required for intracellular survival; thermotolerance (the ability to grow at 37°C), which is a prerequisite for dissemination to visceral organs; and the ability to exist in different forms and to reversibly switch from one to the other during infection122, 123, 124.

Immunity to fungal infections 

Examples of the latter are the dimorphic fungi, which transform from saprobic filamentous moulds to unicellular yeasts in the host. Also, some species of Candida can grow in different forms, such as yeasts, blastospores, pseudohyphae and hyphae, depending on infection sites. Cryptococcus neoformans yeasts become coated with a capsule, and the filamentous fungi (for example, Aspergillus spp., Fusarium spp. and Zygomycota), which are inhaled as unicellular conidia, can transform into branching hyphae in the lungs. Although such morphogenesis is an example of a developmental change, it is distinct from the life cycles that are displayed by other organisms, as there is no evidence that cycling between different morphotypes is obligatory for fungi. Instead, morphological transition, often connected with metabolic flexibility, is a mechanism that some fungi have evolved to adapt to different environments.

Associations between morphogenesis and virulence have long been presumed for dimorphic fungi that are human pathogens, as one morphotype exists in the environment or during commensalism, and others in the host during the disease process125. However, although morphological flexibility could be a key contributor to fungal invasion, no molecular data unambiguously establish a role for fungal morphogenesis as a virulence factor126. In addition, as virulence genes are co-regulated with cell morphogenesis, the ability to switch from yeast to hyphal growth in response to various environmental signals is considered to be inherent to Candida virulence. Both yeast and hyphal forms of fungi clearly have a wide range of attributes that contribute actively to fungal infectivity. Undoubtedly, fungal morphogenesis, through antigenic variability, phenotypic switching and dimorphic transition, implicates the existence of many recognition and effector mechanisms to oppose fungal infectivity at the different body sites.