The cellular and molecular toxicity of sporidesmin

Jordan, T. William

doi:10.1080/00480169.2020.1729268

Cited by 8 publications

(14 citation statements)

References 96 publications

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“…The mechanism of toxicity of sporidesmin, the causative mycotoxin, is believed to be through the generation of reactive oxygen species including superoxide radicals, leading to liver damage [78]. Other modes of action have also been postulated and may warrant further examination [79]. Antioxidants scavenge reactive oxygen species, and research in mice and human cell lines suggest haemoglobin may function as an antioxidant, suppressing oxidative stress and protecting cells from oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep

McRae

Rowe

Johnson

et al. 2021

Genes

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Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, γ-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the β-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit β (HBB) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult β-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

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Section: Discussionmentioning

confidence: 99%

Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep

McRae

Rowe

Johnson

et al. 2021

Genes

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“…This fungus grows rapidly on dead litter at the base of pasture, and spores freely in specific weather conditions of high humidity and ambient temperatures above 12°C, in late summer and autumn. Under these conditions, it produces sporidesmin, a hepatotoxic mycotoxin, which in sufficient concentrations is able to cause hepatobiliary and other tissue damage, but its mechanism of action is not precisely known 3 . The pathogenesis of hepatogenous photosensitisation is based on increased circulating plasma concentrations of the photosensitising agent phytoporphyrin, a normal breakdown product of chlorophyll, following impaired hepatobiliary excretion because of hepatic dysfunction or bile duct lesions.…”

Section: Introductionmentioning

confidence: 99%

First case of pithomycotoxicosis in sheep in the Netherlands

Dijkstra

Harkema

Vellema

2022

Vet Record Case Reports

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Pithomycotoxicosis, commonly known as facial eczema, is a hepatogenous photosensitisation in grazing ruminants caused by intake of sporidesmin‐containing spores of the saprophytic fungus Pithomyces chartarum. Although this is a significant sheep disease in various countries in the world, it is rarely seen in Europe, and has been reported only once in the Netherlands, but in cattle. In October 2019, both sheep and lambs in a flock of 50 breeding sheep showed clinical signs of photosensitisation, including oedematous facial swelling, reddening of eyelids, ulcerative skin lesions, hyperpigmentation, and in some cases icteric sclerae. The combination of clinical signs, seriously elevated glutamate dehydrogenase, gamma‐glutamyl transferase and total bilirubin, necropsy findings, course of events, time of the year, absence of known toxic plants or mycotoxins, strongly suggest that sporidesmin was the most probable cause of this case of hepatogenous photosensitisation, which makes this the first reported case of pithomycotoxicosis in sheep in the Netherlands.

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“…Pithomycotoxicosis (also known as facial eczema [FE]) is a serious liver syndrome in ruminants grazing ryegrass pastures containing spores of the dothideomycete fungus Pseudopithomyces chartarum sensu lato Curtis) [1][2][3]. The spores contain sporidesmin (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Autooxidation of sporidesmin A in the liver induces severe local free radical-induced damage and accumulation of photoreactive chlorophyll degradation byproducts which induce FE. Cholestatic liver damage resulting from consumption of spore-contaminated feed results in impaired reproductive indices and animal productivity [12] well before facial lesions are seen at near end-state pathology [3].…”

Section: Introductionmentioning

confidence: 99%

“…ETPs are a class of secondary metabolites, made only by fungi, that are characterised by the presence of a sulphur-bridged dioxopiperazine ring synthesised from two amino acids by a non-ribosomal peptide synthetase (NRPS). ETP toxicity is attributed to the generation of reactive oxygen species (ROS) through redox cycling and cross-linking to proteins through their cysteine residues which causes cellular damage [3,16]. Putative ETP gene clusters have been found in many ascomycete taxa [17] and include well-characterised examples such as the sirodesmin (sir) [18], gliotoxin (gli) [19], and aspirochlorine (acl) [20] clusters of L. maculans, A. fumigatus, and A. oryzae respectively.…”

Section: Introductionmentioning

confidence: 99%

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Genome sequence ofPseudopithomyces chartarum, causal agent of facial eczema (pithomycotoxicosis) in ruminants, and identification of the putative sporidesmin toxin gene cluster

Suresh

Baten

et al. 2021

Preprint

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Facial eczema (FE) in grazing ruminants is a debilitating liver syndrome induced by ingestion of sporidesmin, a toxin belonging to the epipolythiodioxopiperazine class of compounds. Sporidesmin is produced in spores of the fungus Pseudopithomyces chartarum, a microbe which colonises leaf litter in pastures. New Zealand has a high occurrence of FE in comparison to other countries as animals are fed predominantly on ryegrass, a species that supports high levels of Pse. chartarum spores. The climate is also particularly conducive for Pse. chartarum growth. Here, we present the genome of Pse. chartarum and identify the putative sporidesmin gene cluster. The Pse. chartarum genome was sequenced using single molecule real-time sequencing (PacBio) and gene models identified. Loci containing genes with homology to the aspirochlorine, sirodesmin PL and gliotoxin cluster genes of Aspergillus oryzae, Leptosphaeria maculans and Aspergillus fumigatus, respectively, were identified by tBLASTn. We identified and annotated an epipolythiodioxopiperazine cluster at a single locus with all the functionality required to synthesise sporidesmin.HighlightsThe whole genome of Pseudopithomyces chartarum has been sequenced and assembled.The genome is 39.13 Mb, 99% complete, and contains 11,711 protein coding genes.A putative sporidesmin A toxin (cause of facial eczema) gene cluster is described.The genomes of Pse. chartarum and the Leptosphaerulina chartarum teleomorph differ.Comparative genomics is required to further resolve the Pseudopithomyces clade.

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The cellular and molecular toxicity of sporidesmin

Cited by 8 publications

References 96 publications

Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep

Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep

First case of pithomycotoxicosis in sheep in the Netherlands

Genome sequence ofPseudopithomyces chartarum, causal agent of facial eczema (pithomycotoxicosis) in ruminants, and identification of the putative sporidesmin toxin gene cluster

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