Metal complexes of the mycotoxins sporidesmin A and gliotoxin, investigated by electrospray ionisation mass spectrometry

Woodcock, Jane C; Henderson, William; Miles, Christopher O.

doi:10.1016/s0162-0134(01)00193-3

Cited by 29 publications

(18 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This interconversion forms the basis of the current method for obtaining high purity sporidesmin a (Miles et al 1992 , and Hg 2 +), which were detectable by mass spectrometry (Woodcock et al 2001), consistent with the suggestion that this type of complex may be responsible for the protective effect of zinc salts against facial eczema (Munday 1984b). Figure 5 shows the chemical characteristics of known sporidesmins.…”

Section: The Toxinsupporting

confidence: 76%

A history of facial eczema (pithomycotoxicosis) research

Menna

Smith²,

Miles

2009

New Zealand Journal of Agricultural Research

View full text Add to dashboard Cite

Facial eczema (pithomycotoxicosis), a photosensitisation of ruminants grazing pasture, has been known in New Zealand for over 100 years, but its cause, a toxin produced by a largely saprophytic fungus, Pithomyces chartarum, growing on litter at the base of pasture and sporing profusely under warm moist conditions in late summer and autumn, was found only 50 years ago. As the fungus spores it produces the toxin sporidesmin which, when eaten by sheep, cattle, goats or deer, causes liver injury with inflammation and blockage of bile ducts. Phylloerythrin, a photodynamic breakdown product of chlorophyll, is no longer excreted but circulates in the blood, causing lesions of unpigmented skin when the affected animal is exposed to sunlight. Lesions do not appear until at least a week after sporidesmin has been ingested, and this lag period delayed discovery of the causative agent, first thought to have been an abnormal metabolite of rapidly growing ryegrass. However, before the role of P. chartarum was discovered, the pathology of the disease had been described, toxic extracts had been made from herbage mown from pastures A08061; Online publication date 21 October 2009 Received 8 October 2008 accepted 4 September 2009 associated with facial eczema outbreaks, and the weather conditions preceding outbreaks had been defined. When the causative agent was identified, cultures of P. chartarum on artificial media produced sporidesmin for chemical characterisation and animal dosing trials. Control of facial eczema in the field was first by avoiding toxic pasture, detected by P. chartarum spore counts on herbage, later by reducing P. chartarum pasture populations by spray application of substituted thiabendazole fungicides, and later still by protecting animals with oral doses of zinc at close to toxic levels. Sheep vary widely in their sensitivity to sporidesmin, either under field conditions in facial eczema outbreaks or when dosed orally with sporidesmin, and breeding resistant animals by selection after sporidesmin challenge is the best long-term control method at present. Whilst facial eczema outbreaks have been most severe in New Zealand, the disease has been reported from an increasing number of countries with warm temperate climates in which ruminants are intensively grazed on pasture. The great majority of New Zealand isolates of P. chartarum produce sporidesmin, but varying proportions of those in other countries do not.

show abstract

Section: The Toxinsupporting

confidence: 76%

A history of facial eczema (pithomycotoxicosis) research

Menna

Smith²,

Miles

2009

New Zealand Journal of Agricultural Research

View full text Add to dashboard Cite

show abstract

“…Moreover, additional LFQ proteomic data reveal that in vitro, DTG can cause specific protein aggregation, manifested by heat instability, possibly due to structural alteration to known Zn Zn)-2H + Cl] À , rather than the monoisotopic peak. 24 In addition, we have found that DTG efficiently chelates Zn 2+ from Zn(PAR) 2 (60 mM), in a dose-dependent manner from 60 to 300 mM DTG. Given that Kocyła et al have proposed an effective pK d of 12.15 at pH 7.4 for Zn(PAR) 2 , it is clear that the affinity of DTG for Zn 2+ must equate to, or exceed, this value as Zn 2+ is removed from the Zn(PAR) 2 complex when equimolar amounts of DTG are added to it.…”

Section: +mentioning

confidence: 85%

Systems impact of zinc chelation by the epipolythiodioxopiperazine dithiol gliotoxin inAspergillus fumigatus: a new direction in natural product functionality

et al. 2018

View full text Add to dashboard Cite

Significance to metallomicsDithiol gliotoxin is a near-terminal biosynthetic intermediate from the gliotoxin biosynthetic pathway in the human pathogen Aspergillus fumigatus. Chemically reduced gliotoxin, dithiol gliotoxin (DTG), is revealed as a biological zinc chelator, and conversely, zinc can relieve the hitherto cryptic fungal autotoxicity of DTG. There is a systems-wide impact of zinc chelation by DTG on the fungal proteome, and we suggest it is DTG, as opposed to gliotoxin, which chelates zinc from metalloproteins. Since gliotoxin can be sequestered by both fungi and bacteria, our findings infer a new avenue to interfere with, and exploit, cellular zinc homeostasis in microorganisms. IntroductionGliotoxin and holomycin are microbial natural products, which are produced by fungal and bacterial spp., respectively (Fig. 1). [1][2][3] Both are low molecular mass metabolites, and each contains a disulphide bridge formed by the action of oxidoreductases, namely GliT and HlmI, on the respective dithiol precursor (Fig. 1). [4][5][6] Disulphide bridge formation is essential for microbial self-protection against these reactive dithiol intermediates, and is a pre-requisite for the Major Facilitator Superfamily transporter GliA-mediated secretion of gliotoxin by Aspergillus fumigatus. 5-8Both metabolites are also present as bis-thiomethylated forms, and gliotoxin bis-thiomethyltransferase GtmA converts dithiol gliotoxin (DTG) to bis-dethiobis(methylthio)gliotoxin (BmGT) in A. fumigatus, whereas the origin of the cognate activity against dithiol holomycin in Streptomyces clavuligeris is unknown (Fig. 1). 9,10Bernardo et al. have shown that upon uptake by eukaryotic cells,

show abstract

“…The high energies typically employed in electron ionization (EI) and chemical ionization (CI) mass spectrometric techniques are avoided in ESI-MS, facilitating the observation of m/z values corresponding to molecular ions with minimum or no fragmentation. The technique is suited to solutions containing preformed ions, making it appropriate for inorganic compounds, including systems containing complexes of metals and metalloids [24,25,[27][28][29][30][31][32][33][34]. We have recently used electrospray ionization mass spectrometry [35] (ESI-MS) to identify complexes for naturally occurring amino acids with each of the toxic heavy metals, cadmium, mercury, thallium and lead, and the less-toxic and medicinally relevant [36,37] heavy metal, bismuth.…”

Section: Resultsmentioning

confidence: 99%