Aflatrem: A Tremorgenic Mycotoxin with Acute Neurotoxic Effects

Valdés, James J.; Cameron, Jacqueline E.; Cole, Richard

doi:10.2307/3430148

Cited by 8 publications

(7 citation statements)

References 3 publications

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“…This compound is a specific inhibitor of calcium-dependent ATPase in the sarcoplasmic reticulum altering Ca 2+ levels, which causes an increase in muscle contraction (Riley et al, 1992). The mycotoxin aflatrem, an indol-diterpene also produced by A. flavus, is a potent tremogenic compound known to induce neurological disorders (Yao et al, 1988;Valdes et al, 1985). We found that the levels of CPA production were decreased in the A. flavus veA mutants, and aflatrem production was blocked (Duran et al, 2007).…”

Section: The Role Of Vea In Aspergillus Secondary Metabolismmentioning

confidence: 79%

The VeA regulatory system and its role in morphological and chemical development in fungi

Calvo

2008

Fungal Genetics and Biology

236

266

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Section: The Role Of Vea In Aspergillus Secondary Metabolismmentioning

confidence: 79%

The VeA regulatory system and its role in morphological and chemical development in fungi

Calvo

2008

Fungal Genetics and Biology

236

266

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“…The mechanisms by which tremorgenicity is effected are not yet fully understood but may be related to known neurological effects of aflatrem which include modulation of neurotransmitter release in the central nervous system (36,38) and inhibition of BK channels in the peripheral nervous system (17).…”

mentioning

confidence: 99%

Identification of Two Aflatrem Biosynthesis Gene Loci in Aspergillus flavus and Metabolic Engineering of Penicillium paxilli To Elucidate Their Function

Nicholson

Koulman

Monahan

et al. 2009

Appl Environ Microbiol

134

148

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Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus.

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“…Aflatrem is a neurotoxic tremorgen that causes "stagger disease" in poisoned hosts and is closely related to other mycotoxins such as paxilline or lolitrem (GALLAGHER & HAWKES 1986). By interfering with big potassium (BK) channels, and, gamma amino butyric acid (GABA)-ergic and glutamatergic processes, aflatrem can induce muscle tremors, changes in activity level, and confusion (VALDES & al. 1985, GANT & al.…”

Section: Cluster 18: Manipulation-related Aflatrem-like Indole-diterpmentioning

confidence: 99%

Genetic underpinnings of host manipulation byOphiocordycepsas revealed by comparative transcriptomics

Will

Das

Trinh

et al. 2020

Preprint

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AbstractThe ant-infecting Ophiocordyceps fungi are globally distributed, host manipulating, specialist parasites that drive aberrant behaviors in infected ants, at a lethal cost to the host. An apparent increase in activity and wandering behaviors precedes a final summiting and biting behavior on to vegetation, positioning the manipulated ant in a site beneficial for fungal growth and transmission. Notably, across Ophiocordyceps species and other known host manipulators, the molecular mechanisms underlying behavioral changes remain largely unclear. We explored possible genetic underpinnings of host manipulation by: (i) producing a hybrid assembly of the Ophiocordyceps camponoti-floridani genome, (ii) conducting laboratory infections coupled with RNAseq of both O. camponoti-floridani and its host, Campontous floridanus, and (iii) using these data for a comparative analysis to similar work performed in Ophiocordyceps kimflemingiae and Camponotus castaneus. We propose differentially expressed genes tied to ant neurobiology, odor response, circadian rhythms, and foraging behavior may be the result of putative fungal effectors such as enterotoxins, aflatrem, and mechanisms disrupting nutrition-sensing or caste-identity pathways.

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Aflatrem: A Tremorgenic Mycotoxin with Acute Neurotoxic Effects

Cited by 8 publications

References 3 publications

The VeA regulatory system and its role in morphological and chemical development in fungi

The VeA regulatory system and its role in morphological and chemical development in fungi

Identification of Two Aflatrem Biosynthesis Gene Loci in Aspergillus flavus and Metabolic Engineering of Penicillium paxilli To Elucidate Their Function

Genetic underpinnings of host manipulation byOphiocordycepsas revealed by comparative transcriptomics

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