Temperature during conidiophore development primes Aspergillus fumigatus spore transcriptome for asexual or sexual reproduction.

Abstract

Aspergillus fumigatus is a thermotolerant saprobe found in soils and plant debris worldwide and an important pathogen of humans, causing two million deaths annually. A. fumigatus makes abundant asexual spores (conidia), which are widely distributed by wind and can be inhaled from the environment. In susceptible individuals, inhaled conidia break dormancy, germinate, and grow in the lung, leading to serious disease. Recent work has shown that conidia made at 37°C and 50°C have different morphologies and germination kinetics. While the asexual cycle is well-characterized at 37°C, much less is known about the asexual cycle at 50°C. Here, we combine flow cytometry and transcriptomics to track morphology and gene expression in the hyphae, conidiophores, and conidia of A. fumigatus during asexual development at 37°C or 50°C. We show that the temperature during a narrow time window in late-stage conidiophore development dictates resulting conidial morphology, transcriptional program, and germination kinetics. As expected, conidiation at 37°C resulted in upregulation of brlA, encoding the master regulator of asexual development, and its downstream targets in conidiophores and conidia. Surprisingly, conidiation at 50°C resulted in upregulation of MAT1-1-1, encoding the master regulator of sexual development, and its downstream targets in conidiophores and conidia. Our findings suggest that temperature during late conidiophore development transcriptionally primes conidia for asexual, parasexual, or sexual development, enhancing chances of survival for progeny. Our findings are especially relevant for agricultural compost, where a wide gradient of temperatures exists, abundant A. fumigatus has been isolated, and resistance to antifungals is thought to evolve.IMPORTANCEThe human pathogen Aspergillus fumigatus has been found in natural and agricultural environments around the world. Disease is acquired when susceptible individuals inhale airborne asexual spores from the environment, which in agriculture generally includes proximity to compost and plant debris piles. This work shows that the environmental temperature when A. fumigatus spores are made determines the transcriptomes of those spores, priming them for future asexual or sexual development. The survival of asexual and sexual spores is very different at different temperatures, so these results are important for understanding how this pathogen survives in varied hostile environments. In addition, there are very few antifungal drugs with which to treat A. fumigatus infections, and resistance is increasing, driven in part by agricultural use of fungicides. These results suggest that higher temperatures during asexual spore formation can lead to increased sexual reproduction and greater chances to evolve antifungal resistance.