Surviving the Heat of the Moment: A Fungal Pathogens Perspective

Temperature is a critical parameter continually monitored by microorganisms. The dynamic environments inhabited by microorganisms evoke constant and effective environmental response strategies that have been elaborated over evolutionary time. For example, a significant rise or fall in ambient temperature initiates a stress response in the organism, commonly known as heat-shock or cold-shock responses, respectively. The phenomenon of temperature sensing has long been studied in microorganisms such as bacteria [1], but these mechanisms are only recently being translated to pathogenic fungi. Fungal pathogens inhabit a remarkable diversity of environments and exhibit a dazzling repertoire of life cycles and environmentally contingent cellular processes. Take for example Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus fumigatus. These fungi are found in diverse environments such as pigeon excreta and soil, but retain a common denominator: the ability to grow at 37uC. Loss of genes necessary for high-temperature growth in these pathogens results in attenuated virulence and at times even death [2–4]. Therefore, high-temperature growth is essential for pathogenesis. A classic example is that Saccharomyces cerevisiae clinical isolates are able to grow at higher temperatures (41uC) than laboratory strains, a characteristic important for their survival in mice [5]. Besides governing virulence, temperature regulates many distinct processes. Morphological transitions and growth temperature are linked in the dimorphic fungi, such as H. capsulatum, which grow as filamentous molds at ambient temperature and switch to a yeast form at elevated host temperature [6]. Temperature also controls morphological transitions in the leading fungal pathogen of humans, Candida albicans; though for this organism ambient temperature favors the yeast form, while elevated temperature induces filamentous growth [7]. C. albicans can also switch from a white to opaque cellular state in host niches with lower temperatures, such as skin, facilitating mating [8]. Many genes are simply induced in response to elevated temperatures and do not serve to sense the external stimuli. Generally the consequences of a thermal upshift, as opposed to the temperature itself, provide a signal the cell will react to. This article focuses on how fungi sense and adapt to changing environmental temperature, using S. cerevisiae as a model.