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Global Impact of Ergot Alkaloids
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Global Impact of Ergot Alkaloids

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (15 June 2021) | Viewed by 45097

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. James L. Klotz

E-Mail Website
Guest Editor
USDA-ARS Forage-Animal Production Research Unit Lexington, KY 40546, USA
Interests: ergot alkaloids, livestock, forages, toxicology pharmacology vascular physiology, systems biology

Special Issue Information

Dear Colleagues,

For many years ergot alkaloids have been identified and studied as both problems or toxins to be mitagated and also as potential medical solutions or cures. These comounds have been primarily studied in the medical/pharmaceutical and agricultural fields. Depending on one’s perspective, the impact that ergot alkaloids have had on the progress of human medicine and livestock production can be either positive or negative. The dose or concentration of ergot alkaloid exposure is paramount. This can make the difference from these compounds being implicated in the morbidity and mortality of individuals with St. Anthony’s Fire to being used to treat migraines and post-partum bleeding or being used to maximize plant resistance and persistence and being framed as an animal welfare concern for grazing the livestock. The ethics of ergot alkaloid use is debated to this day, but there is no debating their impacts. Many of the positive and negative issues associated with ergot alkaloids have specific conditions with regional implications, but that does not diminsh the magnitude of impact that these compounds have had on humans, livestock, and plants globally. The focus of this special issue will include original research and review articles that highlight benefits and detriments and successes and failures involving ergot alkloids around the world with deference to regional distinctions. What role have ergot alkaloids played and continue to play in your country, your region, and on your research? 

We all focus on how ergot alkaloids influence (positive or negative) our individual situation. There is a benefit to this shared interest even if the issues with ergot alkaloids don’t directly overlap.

Dr. James L. Klotz
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Ergot alkaloids
  • Toxin
  • Drug development
  • Medicine
  • Livestock
  • Endophyte

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

3 pages, 205 KiB  
Editorial
Global Impact of Ergot Alkaloids
by James L. Klotz
Toxins 2022, 14(3), 186; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14030186 - 03 Mar 2022
Cited by 4 | Viewed by 2503
Abstract
For many years, ergot alkaloids have been considered both a problem to be mitigated and a potential medical cure [...] Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)

Research

Jump to: Editorial, Review

11 pages, 1310 KiB  
Article
Influence of Prolonged Serotonin and Ergovaline Pre-Exposure on Vasoconstriction Ex Vivo
by Eriton E. L. Valente, David L. Harmon and James L. Klotz
Toxins 2022, 14(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14010009 - 23 Dec 2021
Cited by 4 | Viewed by 2507
Abstract
Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate [...] Read more.
Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10−7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10−10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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19 pages, 2856 KiB  
Article
Evolution of the Ergot Alkaloid Biosynthetic Gene Cluster Results in Divergent Mycotoxin Profiles in Claviceps purpurea Sclerotia
by Carmen Hicks, Thomas E. Witte, Amanda Sproule, Tiah Lee, Parivash Shoukouhi, Zlatko Popovic, Jim G. Menzies, Christopher N. Boddy, Miao Liu and David P. Overy
Toxins 2021, 13(12), 861; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13120861 - 02 Dec 2021
Cited by 9 | Viewed by 3747
Abstract
Research into ergot alkaloid production in major cereal cash crops is crucial for furthering our understanding of the potential toxicological impacts of Claviceps purpurea upon Canadian agriculture and to ensure consumer safety. An untargeted metabolomics approach profiling extracts of C. purpurea sclerotia from [...] Read more.
Research into ergot alkaloid production in major cereal cash crops is crucial for furthering our understanding of the potential toxicological impacts of Claviceps purpurea upon Canadian agriculture and to ensure consumer safety. An untargeted metabolomics approach profiling extracts of C. purpurea sclerotia from four different grain crops separated the C. purpurea strains into two distinct metabolomic classes based on ergot alkaloid content. Variances in C. purpurea alkaloid profiles were correlated to genetic differences within the lpsA gene of the ergot alkaloid biosynthetic gene cluster from previously published genomes and from newly sequenced, long-read genome assemblies of Canadian strains. Based on gene cluster composition and unique polymorphisms, we hypothesize that the alkaloid content of C. purpurea sclerotia is currently undergoing adaptation. The patterns of lpsA gene diversity described in this small subset of Canadian strains provides a remarkable framework for understanding accelerated evolution of ergot alkaloid production in Claviceps purpurea. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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24 pages, 8524 KiB  
Article
Mining Indole Alkaloid Synthesis Gene Clusters from Genomes of 53 Claviceps Strains Revealed Redundant Gene Copies and an Approximate Evolutionary Hourglass Model
by Miao Liu, Wendy Findlay, Jeremy Dettman, Stephen A. Wyka, Kirk Broders, Parivash Shoukouhi, Kasia Dadej, Miroslav Kolařík, Arpeace Basnyat and Jim G. Menzies
Toxins 2021, 13(11), 799; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13110799 - 13 Nov 2021
Cited by 6 | Viewed by 2321
Abstract
Ergot fungi (Claviceps spp.) are infamous for producing sclerotia containing a wide spectrum of ergot alkaloids (EA) toxic to humans and animals, making them nefarious villains in the agricultural and food industries, but also treasures for pharmaceuticals. In addition to three classes [...] Read more.
Ergot fungi (Claviceps spp.) are infamous for producing sclerotia containing a wide spectrum of ergot alkaloids (EA) toxic to humans and animals, making them nefarious villains in the agricultural and food industries, but also treasures for pharmaceuticals. In addition to three classes of EAs, several species also produce paspaline-derived indole diterpenes (IDT) that cause ataxia and staggers in livestock. Furthermore, two other types of alkaloids, i.e., loline (LOL) and peramine (PER), found in Epichloë spp., close relatives of Claviceps, have shown beneficial effects on host plants without evidence of toxicity to mammals. The gene clusters associated with the production of these alkaloids are known. We examined genomes of 53 strains of 19 Claviceps spp. to screen for these genes, aiming to understand the evolutionary patterns of these genes across the genus through phylogenetic and DNA polymorphism analyses. Our results showed (1) varied numbers of eas genes in C. sect. Claviceps and sect. Pusillae, none in sect. Citrinae, six idt/ltm genes in sect. Claviceps (except four in C. cyperi), zero to one partial (idtG) in sect. Pusillae, and four in sect. Citrinae, (2) two to three copies of dmaW, easE, easF, idt/ltmB, itd/ltmQ in sect. Claviceps, (3) frequent gene gains and losses, and (4) an evolutionary hourglass pattern in the intra-specific eas gene diversity and divergence in C. purpurea. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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8 pages, 1092 KiB  
Communication
Using On-Farm Monitoring of Ergovaline and Tall Fescue Composition for Horse Pasture Management
by Krista La Moen Lea and S. Ray Smith
Toxins 2021, 13(10), 683; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13100683 - 25 Sep 2021
Cited by 2 | Viewed by 1763
Abstract
Central Kentucky horse pastures contain significant populations of tall fescue (Schedonorus arundinacea (Schreb.) Dumort) infected with an endophyte (Epichloë coenophialum (Morgan-Jones and Gams) Bacon and Schardl) known to produce several ergot alkaloids, with ergovaline in the highest concentration. While most classes [...] Read more.
Central Kentucky horse pastures contain significant populations of tall fescue (Schedonorus arundinacea (Schreb.) Dumort) infected with an endophyte (Epichloë coenophialum (Morgan-Jones and Gams) Bacon and Schardl) known to produce several ergot alkaloids, with ergovaline in the highest concentration. While most classes of horses are not adversely affected by average levels of ergovaline in pastures, late term pregnant mares have a low tolerance to ergovaline and the related ergot alkaloids. Endophyte-infected tall fescue has been known to cause prolonged gestation, thickened placenta, dystocia, agalactia, and foal and mare mortality. The University of Kentucky Horse Pasture Evaluation Program utilizes ergovaline and endophyte testing, as well as pasture species composition, to calculate ergovaline in the total diet in broodmare pastures. This data is used to develop detailed management recommendations for individual pastures. Application of these recommendations has led to reduced tall fescue toxicity symptoms on these farms, as well as improved pasture management and improved forage quality and quantity. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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12 pages, 2435 KiB  
Article
Vasoactive Effects of Acute Ergot Exposure in Sheep
by Rossalin Yonpiam, Jair Gobbet, Ashok Jadhav, Kaushik Desai, Barry Blakley and Ahmad Al-Dissi
Toxins 2021, 13(4), 291; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13040291 - 20 Apr 2021
Cited by 4 | Viewed by 2259
Abstract
Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects [...] Read more.
Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10−6 M; Exp EC50 = 1.079 × 10−6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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16 pages, 3352 KiB  
Article
Effects of Tall Fescue Endophyte Type and Dopamine Receptor D2 Genotype on Cow-Calf Performance during Late Gestation and Early Lactation
by Sarah A. Wilbanks, Susan Maggie Justice, Thomas West, James L. Klotz, John G. Andrae and Susan K. Duckett
Toxins 2021, 13(3), 195; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030195 - 09 Mar 2021
Cited by 3 | Viewed by 2005
Abstract
Grazing endophyte-infected, toxic tall fescue reduces cow/calf production; therefore, this study examines alternate strategies such as use of novel endophyte fescue varieties during late gestation and early lactation or genetic selection of resistant cows. Pregnant cows (n = 75) were randomly assigned to [...] Read more.
Grazing endophyte-infected, toxic tall fescue reduces cow/calf production; therefore, this study examines alternate strategies such as use of novel endophyte fescue varieties during late gestation and early lactation or genetic selection of resistant cows. Pregnant cows (n = 75) were randomly assigned to fescue endophyte type: 1) endophyte-infected ergot alkaloid producing tall fescue (E+) or 2) novel endophyte-infected, non-toxic tall fescue (NOV) within maternal (A|A, n = 38 and G|G, n = 37) DRD2 genotype to examine changes in cow/calf performance and milk production during late gestation and early lactation. Grazing E+ fescue pastures during late gestation reduced cow body weight gain but did not alter calf birth weight compared to NOV. Milk production and calf ADG during the first 30 day of lactation were lower for E+ than NOV. The calving rate was reduced, but not calving interval for E+ cows. The adjusted 205-day weight of calves was lower in those grazing E+ with their dams compared to NOV. There were no interactions between DRD2 genotype and fescue endophyte type indicating that genotype was not associated with response to E+ fescue in this study. Overall, grazing NOV tall fescue pastures rather than E+ during critical stages of production improved cow gain during late gestation, calving rate, early milk production and calf growth. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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16 pages, 1667 KiB  
Article
Non-Transgenic CRISPR-Mediated Knockout of Entire Ergot Alkaloid Gene Clusters in Slow-Growing Asexual Polyploid Fungi
by Simona Florea, Jolanta Jaromczyk and Christopher L. Schardl
Toxins 2021, 13(2), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020153 - 16 Feb 2021
Cited by 11 | Viewed by 2597
Abstract
The Epichloë species of fungi include seed-borne symbionts (endophytes) of cool-season grasses that enhance plant fitness, although some also produce alkaloids that are toxic to livestock. Selected or mutated toxin-free endophytes can be introduced into forage cultivars for improved livestock performance. Long-read genome [...] Read more.
The Epichloë species of fungi include seed-borne symbionts (endophytes) of cool-season grasses that enhance plant fitness, although some also produce alkaloids that are toxic to livestock. Selected or mutated toxin-free endophytes can be introduced into forage cultivars for improved livestock performance. Long-read genome sequencing revealed clusters of ergot alkaloid biosynthesis (EAS) genes in Epichloë coenophiala strain e19 from tall fescue (Lolium arundinaceum) and Epichloë hybrida Lp1 from perennial ryegrass (Lolium perenne). The two homeologous clusters in E. coenophiala—a triploid hybrid species—were 196 kb (EAS1) and 75 kb (EAS2), and the E. hybrida EAS cluster was 83 kb. As a CRISPR-based approach to target these clusters, the fungi were transformed with ribonucleoprotein (RNP) complexes of modified Cas9 nuclease (Cas9-2NLS) and pairs of single guide RNAs (sgRNAs), plus a transiently selected plasmid. In E. coenophiala, the procedure generated deletions of EAS1 and EAS2 separately, as well as both clusters simultaneously. The technique also gave deletions of the EAS cluster in E. hybrida and of individual alkaloid biosynthesis genes (dmaW and lolC) that had previously proved difficult to delete in E. coenophiala. Thus, this facile CRISPR RNP approach readily generates non-transgenic endophytes without toxin genes for use in research and forage cultivar improvement. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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Graphical abstract

21 pages, 2073 KiB  
Article
Evaluation of Resistance to Fescue Toxicosis in Purebred Angus Cattle Utilizing Animal Performance and Cytokine Response
by Daniel H. Poole, Kyle J. Mayberry, McKayla Newsome, Rebecca K. Poole, Justine M Galliou, Piush Khanal, Matthew H. Poore and Nick V. L. Serão
Toxins 2020, 12(12), 796; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120796 - 14 Dec 2020
Cited by 6 | Viewed by 2414
Abstract
Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue; however, varying symptomatic responses potentially imply genetic tolerance to the syndrome. It was hypothesized that a subpopulation of animals within a herd would develop tolerance to ergot alkaloid toxicity. Therefore, [...] Read more.
Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue; however, varying symptomatic responses potentially imply genetic tolerance to the syndrome. It was hypothesized that a subpopulation of animals within a herd would develop tolerance to ergot alkaloid toxicity. Therefore, the goals of this study were to develop selection criteria to identify tolerant and susceptible animals within a herd based on animal performance, and then examine responsive phenotypic and cytokine profiles to fescue toxicosis. Angus cows grazed endophyte-infected tall fescue at two locations for 13 weeks starting in mid-April 2016. Forage measurements were collected to evaluate ergot alkaloid exposure during the study. A post hoc analysis of animal performance was utilized to designate cattle into either tolerant or susceptible groups, and weekly physiological measurements and blood samples were collected to evaluate responses to chronic exposure to endophyte-infected tall fescue. Findings from this study support the proposed fescue toxicosis selection method formulated herein, could accurately distinguish between tolerant and susceptible animals based on the performance parameters in cattle chronically exposed to ergot alkaloids, and provides evidence to warrant additional analysis to examine the impact of ergot alkaloids on immune responsiveness in cattle experiencing fescue toxicosis. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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17 pages, 3782 KiB  
Article
Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers
by Taylor B. Ault-Seay, Emily A. Melchior-Tiffany, Brooke A. Clemmons, Juan F. Cordero, Gary E. Bates, Michael D. Flythe, James L. Klotz, Huihua Ji, Jack P. Goodman, Kyle J. McLean and Phillip R. Myer
Toxins 2020, 12(12), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120744 - 26 Nov 2020
Cited by 4 | Viewed by 2692
Abstract
Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. [...] Read more.
Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (n = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E−) tall fescue seed, with (P+) or without (P−) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (p < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (p < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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18 pages, 1662 KiB  
Article
Ergot and Ergot Alkaloids in Cereal Grains Intended for Animal Feeding Collected in Slovenia: Occurrence, Pattern and Correlations
by Janja Babič, Gabrijela Tavčar-Kalcher, Franci Aco Celar, Katarina Kos, Matjaž Červek and Breda Jakovac-Strajn
Toxins 2020, 12(11), 730; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12110730 - 21 Nov 2020
Cited by 17 | Viewed by 2555
Abstract
This four-year study reports the occurrence of ergot alkaloids (EAs) in cereals intended for animal feeding collected in Slovenia. A total of 517 samples of cereals were analysed using liquid chromatography-tandem mass spectrometry for the presence of EAs. The sample set included wheat, [...] Read more.
This four-year study reports the occurrence of ergot alkaloids (EAs) in cereals intended for animal feeding collected in Slovenia. A total of 517 samples of cereals were analysed using liquid chromatography-tandem mass spectrometry for the presence of EAs. The sample set included wheat, rye, triticale, oat, spelt and barley. The study revealed that 17% of the analysed cereal samples were contaminated with at least one ergot alkaloid. EAs have two epimeric forms: -ine and -inine. The incidence rates of the -ine and -inine forms in the analysed samples were 16% and 15%, respectively. The highest contamination rates were observed in rye (54%), oat (50%) and spelt (30%), where the highest mean concentrations of total EAs were also determined (502 µg/kg, 594 µg/kg and 715 µg/kg, respectively). However, the highest concentrations of total EAs were found in wheat and rye (4217 µg/kg and 4114 µg/kg, respectively). The predominant EAs were ergometrine, ergosine and ergocristinine. The occurrence of six or more ergot alkaloids was observed in 49% of the positive samples. A weak correlation (p = 0.284) in the positive samples was found between the mass of sclerotia and the total concentrations of EAs using the Spearman correlation coefficient. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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19 pages, 4428 KiB  
Article
Novel Ergot Alkaloids Production from Penicillium citrinum Employing Response Surface Methodology Technique
by Memuna Ghafoor Shahid, Muhammad Nadeem, Ahmed Gulzar, Muhammad Saleem, Hafeez ur Rehman, Gul Zareen Ghafoor, Muhammad Umar Hayyat, Laila Shahzad, Rabia Arif and Rubina Nelofer
Toxins 2020, 12(7), 427; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12070427 - 29 Jun 2020
Cited by 5 | Viewed by 3339
Abstract
Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species Penicillium citrinum. To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of [...] Read more.
Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species Penicillium citrinum. To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of Penicillium was improved using physical (ultraviolet (UV) and chemical (ethyl methane sulfonate (EMS) treatments to get the maximum yield of ergot alkaloids through surface culture fermentation technique. After improving the strain, survival rate of colonies of Penicillium citrinum treated with UV and EMS was observed. Only 2.04% living colonies were observed after 150 min of exposure of Penicillium citrinum in UV light and 3.2% living colonies were observed after 20 min of the exposure in EMS. The mutated strains of Penicillium citrinum were screened for their production of ergot alkaloids and after fermentation experiments, maximum yield was obtained from PCUV-4 and PCEMS-1 strains. After strain improvement, Plackett–Burman design (PBD) and Box–Behnken design (BBD) of RSM were employed and 10-fold yield enhancement (35.60 mg/100 mL) of ergot alkaloids was achieved. This enhancement in yield of ergot alkaloids proved the positive impacts of RSM and UV on the yield of ergot alkaloids. The study provides a cost effective, economical and sustainable process to produce medically important ergot alkaloids which can be used in various pharmaceutical formulations to treat human diseases. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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Review

Jump to: Editorial, Research

9 pages, 499 KiB  
Review
The Usage of Ergot (Claviceps purpurea (fr.) Tul.) in Obstetrics and Gynecology: A Historical Perspective
by Aleksander Smakosz, Wiktoria Kurzyna, Michał Rudko and Mateusz Dąsal
Toxins 2021, 13(7), 492; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13070492 - 15 Jul 2021
Cited by 9 | Viewed by 6009
Abstract
In the past centuries consumption of bread made of ergot-infected flour resulted in mass poisonings and miscarriages. The reason was the sclerotia of Claviceps purpurea (Fr.) Tul.—a source of noxious ergot alkaloids (ergotamine and ergovaline). The authors have searched the 19th century medical [...] Read more.
In the past centuries consumption of bread made of ergot-infected flour resulted in mass poisonings and miscarriages. The reason was the sclerotia of Claviceps purpurea (Fr.) Tul.—a source of noxious ergot alkaloids (ergotamine and ergovaline). The authors have searched the 19th century medical literature in order to find information on the following topics: dosage forms of drugs based on ergot and their application in official gynecology and obstetrics. The authors also briefly address the relevant data from the previous periods as well as the 20th century research on ergot. The research resulted in a conclusion that applications of ergot in gynecology and obstetrics in the 19th century were limited to controlling excessive uterine bleeding and irregular spasms, treatment of fibrous tumors of the uterus, and prevention of miscarriage, abortion, and amenorrhoea. The most common dosage forms mentioned in the works included in our review were the following: tinctures, water extracts (Wernich’s and Squibb’s watery extract of ergot), pills, and powders. The information documented in this paper will be helpful for further research and helpful in broadening the understanding of the historical application of the described controversial crude drugs. Ergot alkaloids were widely used in obstetrics, but in modern times they are not used in developed countries anymore. They may, however, play a significant role in developing countries where, in some cases, they can be used as an anti-hemorrhage agent during labor. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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21 pages, 739 KiB  
Review
The Impact of Alkaloid-Producing Epichloë Endophyte on Forage Ryegrass Breeding: A New Zealand Perspective
by Colin Eady
Toxins 2021, 13(2), 158; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020158 - 18 Feb 2021
Cited by 11 | Viewed by 3615
Abstract
For 30 years, forage ryegrass breeding has known that the germplasm may contain a maternally inherited symbiotic Epichloë endophyte. These endophytes produce a suite of secondary alkaloid compounds, dependent upon strain. Many produce ergot and other alkaloids, which are associated with both insect [...] Read more.
For 30 years, forage ryegrass breeding has known that the germplasm may contain a maternally inherited symbiotic Epichloë endophyte. These endophytes produce a suite of secondary alkaloid compounds, dependent upon strain. Many produce ergot and other alkaloids, which are associated with both insect deterrence and livestock health issues. The levels of alkaloids and other endophyte characteristics are influenced by strain, host germplasm, and environmental conditions. Some strains in the right host germplasm can confer an advantage over biotic and abiotic stressors, thus acting as a maternally inherited desirable ‘trait’. Through seed production, these mutualistic endophytes do not transmit into 100% of the crop seed and are less vigorous than the grass seed itself. This causes stability and longevity issues for seed production and storage should the ‘trait’ be desired in the germplasm. This makes understanding the precise nature of the relationship vitally important to the plant breeder. These Epichloë endophytes cannot be ‘bred’ in the conventional sense, as they are asexual. Instead, the breeder may modulate endophyte characteristics through selection of host germplasm, a sort of breeding by proxy. This article explores, from a forage seed company perspective, the issues that endophyte characteristics and breeding them by proxy have on ryegrass breeding, and outlines the methods used to assess the ‘trait’, and the application of these through the breeding, production, and deployment processes. Finally, this article investigates opportunities for enhancing the utilisation of alkaloid-producing endophytes within pastures, with a focus on balancing alkaloid levels to further enhance pest deterrence and improving livestock outcomes. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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19 pages, 1064 KiB  
Review
Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis
by Ryan S. Mote and Nikolay M. Filipov
Toxins 2020, 12(10), 633; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12100633 - 01 Oct 2020
Cited by 5 | Viewed by 2800
Abstract
Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The ‘omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed [...] Read more.
Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The ‘omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed our understanding of disease mechanisms and the multi-dimensional interaction between environmental stressors and host physiology through data integration into multi-dimensional analyses, i.e., integrative interactomics. This review focuses on the use of high-throughput technologies in farm animal research, including health- and toxicology-related papers. Although limited, we highlight recent animal agriculture-centered reports from the integrative multi-‘omics movement. We provide an example with fescue toxicosis, an economically costly disease affecting grazing livestock, and describe how integrative interactomics can be applied to a disease with a complex pathophysiology in the pursuit of novel treatment and management approaches. We outline how ‘omics techniques have been used thus far to understand fescue toxicosis pathophysiology, lay out a framework for the fescue toxicosis integrome, identify some challenges we foresee, and offer possible means for addressing these challenges. Finally, we briefly discuss how the example with fescue toxicosis could be used for other agriculturally important animal health and welfare problems. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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