Triazole Priming as an Adaptive Response and Gateway to Resistance in Aspergillus fumigatus.

Invasive aspergillosis (IA), caused predominantly by Aspergillus fumigatus, is the most common opportunistic mold infection in immunocompromised patients. Resistance of A. fumigatus to triazoles has been increasingly reported, leading to poor outcomes of IA to the front-line azoles. Triazole resistance is in part driven by exposure to agricultural azoles through mechanisms that are poorly understood beyond mutations in ergosterol biosynthetic genes. Priming is defined as a process in which prior exposures to sublethal stressful stimuli, such as antimicrobial drugs, can enhance the ability of pathogens to withstand reexposure to the same or other stressors. Here, we describe, for the first time, triazole priming, where exposure of conidia of three A. fumigatus strains to subinhibitory concentrations of either agricultural (tebuconazole difenoconazole, epoxiconazole) or medical triazoles (voriconazole) increases germination and growth during subsequent reexposure to subinhibitory triazole challenge. We demonstrate that priming in A. fumigatus is class specific to triazoles, is not confined to a particular isolate, and is retained for extended periods in primed dormant conidia, but is not transferred to subsequent generations. Furthermore, azole priming at subinhibitory triazole concentrations increased the frequency of development of stable resistance development at inhibitory triazole exposures. Triazole priming could have far-reaching clinical implications in generating resistance due to the widespread use of agricultural triazoles or breakthrough IA in patients with subtherapeutic serum levels of azoles.

Fungal Priming: Prepare or Perish.

Priming (also referred to as acclimation, acquired stress resistance, adaptive response, or cross-protection) is defined as an exposure of an organism to mild stress that leads to the development of a subsequent stronger and more protective response. This memory of a previously encountered stress likely provides a strong survival advantage in a rapidly shifting environment. Priming has been identified in animals, plants, fungi, and bacteria. Examples include innate immune priming and transgenerational epigenetic inheritance in animals and biotic and abiotic stress priming in plants, fungi, and bacteria. Priming mechanisms are diverse and include alterations in the levels of specific mRNAs, proteins, metabolites, and epigenetic changes such as DNA methylation and histone acetylation of target genes.

Development of Novel Forms of Fungal Art Using Aspergillus nidulans.

Fungi are embedded in human culture, tradition, and art, and have featured as inspirational and visual motifs. Psychedelic and medicinal mushrooms have been sculpted, painted, and ingested by our ancestors since prehistory. In modern times, the growing divide between the arts and sciences has delegated fungal art to a niche activity, with the bulk of the focus being on mycelium as a biomaterial. A collaboration between a multidisciplinary artist and a research laboratory, specializing in the molecular study of Aspergillus molds, has allowed us to develop new forms of mycelial art. We describe in detail the development of fungal art techniques using nutrient-rich agar containing Aspergillus nidulans conidia spotted on glass acrylic surfaces or impregnated onto etched acrylic blocks. This approach generates visually and temporally dynamic artwork that is user-friendly, safe, relatively resistant to contamination and easily scalable. Moreover, it offers countless avenues of artistic development based on the diversity of colors, textures and shapes afforded by different fungal species.