Coevolution of morphology and virulence in Candida species

Abstract

Many of the major human fungal pathogens are known to undergo morphological changes, which in certain cases are associated with virulence. Although there has been an intense research focus on morphology in fungi, very little is known about how morphology evolved in conjunction with a variety of other virulence properties. However, several recent important discoveries, primarily in Candida species, are beginning to shed light on this important area and answer many longstanding questions. In this minireview, we first provide a description of the major fungal morphologies, as well as the roles of morphology and morphology-associated gene expression in virulence. Next, focusing largely on Candida species, we examine the evolutionary relationships among specific morphological forms. Finally, drawing on recent findings, we begin to address the question of how specific morphological changes came to be associated with virulence of Candida species during evolution.

Fig. 1.

Major morphologies of human fungal pathogens. (Top) Images of C. albicans cells as visualized by differential interference contrast (DIC) microscopy (bar = 10 μm). (Bottom) Schematic representation of each morphology.

Fig. 2.

Model for evolution of morphology and virulence in Candida species. In the mammalian host reservoir, the yeast form is believed to have adapted for colonization of mucosal cell surfaces in the oral cavity, gastrointestinal tract, and/or vagina. Stepwise evolution from yeast to pseudohyphae to hyphae is believed to be associated with increased virulence gene expression and the development of a variety of virulence properties. As an evolutionarily intermediate morphology, pseudohyphae were initially most likely important for promoting nutrient scavenging and motility in the host environment, although they may eventually have evolved to possess a weaker version of several virulence properties associated with hyphae. It is important to note that these morphological transitions are typically reversible and that the yeast form has also evolved to play a number of important roles in the virulence process. While the precise time points at which each morphology came to be associated with specific virulence properties are unknown, the entire time since the divergence of C. albicans (which is likely the most highly evolved Candida species) from the nonpathogenic model yeast S. cerevisiae is approximately 841 million years (54). Similar to S. cerevisiae, the most primitive Candida species are likely to have possessed a very weak ability to form pseudohyphae in response to a very limited set of environmental cues. Over evolution, Candida species are believed to have acquired the ability to form pseudohyphae more frequently and in response to a broader range of conditions in the host environment. Finally, it is important to bear in mind that not all fungal pathogens are likely to have evolved virulence properties in association with morphological shifts, as depicted in the model.