Trans-2-hexenal downregulates several pathogenicity genes of Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats.

White-nose syndrome is an emergent wildlife disease that has killed millions of North American bats. It is caused by Pseudogymnoascus destructans, a cold-loving, invasive fungal pathogen that grows on bat tissues and disrupts normal hibernation patterns. Previous work identified trans-2-hexenal as a fungistatic volatile compound that potentially could be used as a fumigant against P. destructans in bat hibernacula. To determine the physiological responses of the fungus to trans-2-hexenal exposure, we characterized the P. destructans transcriptome in the presence and absence of trans-2-hexenal. Specifically, we analyzed the effects of sublethal concentrations (5 µmol/L, 10 µmol/L, and 20 µmol/L) of gas-phase trans-2-hexenal of the fungus grown in liquid culture. Among the three treatments, a total of 407 unique differentially expressed genes (DEGs) were identified, of which 74 were commonly affected across all three treatments, with 44 upregulated and 30 downregulated. Downregulated DEGs included several probable virulence genes including those coding for a high-affinity iron permease, a superoxide dismutase, and two protein-degrading enzymes. There was an accompanying upregulation of an ion homeostasis gene, as well as several genes involved in transcription, translation, and other essential cellular processes. These data provide insights into the mechanisms of action of trans-2-hexenal as an anti-fungal fumigant that is active at cold temperatures and will guide future studies on the molecular mechanisms by which six carbon volatiles inhibit growth of P. destructans and other pathogenic fungi.

Pseudogymnoascus destructans: Causative Agent of White-Nose Syndrome in Bats Is Inhibited by Safe Volatile Organic Compounds.

White-nose syndrome (WNS) is caused by Pseudogymnoascus destructans, a psychrophilic fungus that infects hibernating bats and has caused a serious decline in some species. Natural aroma compounds have been used to control growth of fungal food storage pathogens, so we hypothesized that a similar strategy could work for control of P. destructans. The effectiveness of exposure to low concentrations of the vapor phase of four of these compounds was tested on mycelial plugs and conidiospores at temperatures of 5, 10 and 15 °C. Here we report the efficacy of vapor phase mushroom alcohol (1-octen-3-ol) for inhibiting mycelial and conidiospore growth of P. destructans at 0.4 and 0.8 µmol/mL and demonstrate that the R enantiomer of this compound is more effective than the S enantiomer, supporting the finding that biological systems can be sensitive to stereochemistry. Further, we report that vapor phase leaf aldehyde (trans-2-hexenal), a common aroma compound associated with cut grass odors and also the major volatile compound in extra virgin olive oil, is more effective than mushroom alcohol. At 0.05 µmol/mL, trans-2-hexenal is fungicidal to both conidiospores and mycelia of P. destructans.

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid.

Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only l-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.