Evidence for the Natural Toxins from the Mushroom <i>Trogia venenata</i> as a Cause of Sudden Unexpected Death in Yunnan Province, China

Zhou, Zhong‐Yu; Shi, Guoqing; Fontaine, Robert E.; Wei, Kun; Feng, Tao; Wang, Fang; Wang, Gangqiang; Qu, Yuanzhi; Li, Zhenghui; Dong, Zhibao; Zhu, Hua‐Jie; Yang, Zhu‐Liang; Zeng, Guang; Liu, Ji‐Kai

doi:10.1002/anie.201106502

Cited by 57 publications

(22 citation statements)

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“…The experimental animal studies have one key similarity to the human cases. In mice a 1.6 fold increase in CK was seen after 3 daily sub-lethal doses while CK and other muscle-related enzymes (myoglobin, and AST) were elevated in family contacts of SUD cases that ate T. venenata [31]. However, the experimental study examined only CK.…”

Section: Discussionmentioning

confidence: 92%

“…In particular, in villages with prior SUD clusters eating the mushroom was tantamount to admitting non-compliance with official warnings. Indeed, a collaborator identified the toxic amino acid in the postmortem heart blood from a single SUD case for which family members denied that the deceased was exposed to T. venenata [31]. Our data on the quantity and timing of the exposure to T. venenata was very sparse and had excessive variability in amount and frequency of exposure.…”

Section: Discussionmentioning

confidence: 94%

“…Our epidemiologic observations have led to toxicological research which has identified from T. venenata , 2 amino acids (2 R -amino-4 S -hydroxy-5-hexynoic acid and 2 R -amino-5-hexynoic acid) that differ by one hydroxyl group [31]. Both are fatally toxic to mice.…”

Section: Discussionmentioning

confidence: 99%

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Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

et al. 2012

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IntroductionSince the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006–2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms.MethodsWe established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease.ResultsWe identified 33 SUD, a 73% decline from 2002–2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata–exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test).DiscussionEpidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 94%

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Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

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“…Altered levels of creatine and GAA have been shown to cause neurological disorders [50]. GBA has also previously been isolated from the fungus Trogia venenata, which has been implicated in causing sudden deaths in Yunnan, China [51]. …”

Section: Resultsmentioning

confidence: 99%

Species-specific ant brain manipulation by a specialized fungal parasite

et al. 2014

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BackgroundA compelling demonstration of adaptation by natural selection is the ability of parasites to manipulate host behavior. One dramatic example involves fungal species from the genus Ophiocordyceps that control their ant hosts by inducing a biting behavior. Intensive sampling across the globe of ants that died after being manipulated by Ophiocordyceps suggests that this phenomenon is highly species-specific. We advance our understanding of this system by reconstructing host manipulation by Ophiocordyceps parasites under controlled laboratory conditions and combining this with field observations of infection rates and a metabolomics survey.ResultsWe report on a newly discovered species of Ophiocordyceps unilateralis sensu lato from North America that we use to address the species-specificity of Ophiocordyceps-induced manipulation of ant behavior. We show that the fungus can kill all ant species tested, but only manipulates the behavior of those it infects in nature. To investigate if this could be explained at the molecular level, we used ex vivo culturing assays to measure the metabolites that are secreted by the fungus to mediate fungus-ant tissue interactions. We show the fungus reacts heterogeneously to brains of different ant species by secreting a different array of metabolites. By determining which ion peaks are significantly enriched when the fungus is grown alongside brains of its naturally occurring host, we discovered candidate compounds that could be involved in behavioral manipulation by O. unilateralis s.l.. Two of these candidates are known to be involved in neurological diseases and cancer.ConclusionsThe integrative work presented here shows that ant brain manipulation by O. unilateralis s.l. is species-specific seemingly because the fungus produces a specific array of compounds as a reaction to the presence of the host brain it has evolved to manipulate. These studies have resulted in the discovery of candidate compounds involved in establishing behavioral manipulation by this specialized fungus and therefore represent a major advancement towards an understanding of the molecular mechanisms underlying this phenomenon.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-014-0166-3) contains supplementary material, which is available to authorized users.

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“…Recent intensive epidemiological and toxicological investigations identified the mushroom Trogia venenata as the lead culprit (11-15, 18, 20). Specifically, two unusual toxic amino acids, 2R-amino-4S-hydroxy-5-hexynoic acid and 2R-amino-5-hexynoic acid, in T. venenata have shown to be capable of causing hypoglycemia in mice (12,20), which could lead to cardiac arrest and SUDs in humans. However, the two toxic amino acids in T. venenata could not explain all SUD cases (13)(14)(15) and questions remain about what other factor(s) in T. venenata or from other sources could have contributed to these deaths.…”

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confidence: 99%

Evidence against Barium in the Mushroom Trogia venenata as a Cause of Sudden Unexpected Deaths in Yunnan, China

Zhang

et al. 2012

Appl Environ Microbiol

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Evidence for the Natural Toxins from the Mushroom Trogia venenata as a Cause of Sudden Unexpected Death in Yunnan Province, China

Cited by 57 publications

References 16 publications

Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

Species-specific ant brain manipulation by a specialized fungal parasite

Evidence against Barium in the Mushroom Trogia venenata as a Cause of Sudden Unexpected Deaths in Yunnan, China

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