Thermotolerance and virulence ofAspergillus fumigatus: role of the fungal nucleolus

Abstract

The ability to thrive at 37 degrees C is characteristic of all human pathogens and has long been suspected to play a role in the pathogenesis of aspergillosis. As a thermotolerant fungus, Aspergillus fumigatus is capable of growth at temperatures that approach the upper limit for all eukaryotes, suggesting that the organism has evolved unique mechanisms of stress resistance that may be relevant to its ability to adapt to the stress of growth in the host. High temperature is a strain on many biological systems, particularly those involved in complex macromolecular assemblies such as ribosomes. This review will discuss the relationship between thermotolerance and virulence in pathogenic fungi, emphasizing the link to ribosome biogenesis in A. fumigatus. Future work in this area will help determine how rapid growth is accomplished at elevated temperature and may offer new avenues for the development of novel antifungals that disrupt thermotolerant ribosome assembly.

Effects of a Defective Endoplasmic Reticulum-Associated Degradation Pathway on the Stress Response, Virulence, and Antifungal Drug Susceptibility of the Mold Pathogen Aspergillus fumigatus

“…The radial growth rate of the ⌬hrdA mutant was impaired at 37°C and above (Fig. 5), suggesting a role for HrdA in the well-known thermotolerance of the fungus (31). As previously reported, the ⌬derA mutant did not show this increase in thermosensitivity (7).…”

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…Other traits of A. fumigatus that enable its pathogenic prowess include its capacity to withstand stress, its small conidial size, and its ability to produce damaging enzymes and toxins. A. fumigatus has the capacity to withstand harsh environmental stresses, including high temperatures of up to 70°C (18,52). The heat shock response of this fungus has been the subject of in-depth investigations (2,154,418).…”

Aspergillus fumigatus: virulence genes in a street-smart mold

“…fumigatus resides in compost, a dynamic environment that undergoes wide fluctuations in temperature as a consequence of intense microbial activity. The ability of A. fumigatus to thrive in this niche requires a substantial level of thermotolerance that has been speculated to contribute to virulence [9][10][11]. Although A. fumigatus displays a distinct pattern of gene expression at 37°C [12], only three genes have been demonstrated to be necessary for thermotolerant growth: the ribosome biogenesis protein CgrA [13], the O-mannosyltransferase Pmt1 [14] and a protein of unknown function, ThtA [15].…”