Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research

Hydrogen sulfide (H(2)S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H(2)S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H(2)S is known to cause brain damage, leading to neurodegeneration and long‐term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H(2)S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H(2)S concentrations. This review focuses on the neuropathology of high acute H(2)S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H(2)S‐induced neurodegeneration