13.4 Fungal toxins: food contamination and deterioration

We all know that a few species of mushrooms are poisonous and many fungi produce secondary metabolites, some of which are known as fungal toxins (see the section on Secondary metabolism in Chapter 10; CLICK HERE to view the page). The adaptive significance of toxins in fungi has been given rather little attention, though it is evident that toxin production is scattered across the entire Kingdom and must have evolved independently several times in evolutionary history. An obvious possible function for toxins is to act as a deterrent to the many animals that might otherwise eat the mushrooms or other fungal structures (see the section on Fungi in food webs in Chapter 11; CLICK HERE to view the page) (Wong, 2013; Singh et al., 2014).

Wild opossums (Didelphis virginiana) became ill after eating the toxic mushroom Amanita muscaria (Fly Agaric), and subsequently developed an aversion to the fungus (Camazine, 1983). It has been argued that such a function leads to the expectation that poisonous mushrooms should signal their hazard in some way, and the ‘red cap with white spots’ of A. muscaria could be cited as an example of warning colouration. However, this does not seem to be the case. Analysis of ecological and morphological traits associated with edible and poisonous mushrooms showed that the poisonous ones were not more colourful than edible mushrooms, but were more likely to have distinctive odours (and perhaps flavours). Raising the interesting possibility that poisonous mushrooms have evolved warning odours/flavours as antifeedants to enhance avoidance learning by fungivores, in contrast to the warning colouration used by poisonous animals to signal ‘avoid me’ to potential predators (Sherratt, Wilkinson & Bain, 2005). There are dangers in this line of argument: it is close to being anthropomorphic (viewing animal behaviour in human terms), and it may be taken to imply that fungal toxins are produced only by mushroom fungi and/or that fungal toxins are aimed specifically at animals. The fly agaric is a remarkable mushroom in many respects. With its relative A. pantherina it is responsible for poisoning in man characterised by central nervous system dysfunction, with ibotenic acid and muscimol being the active components. However, A. muscaria contains other substances responsible for psychotropic effects in man, and it has been used since ancient times for mystical purposes by witch doctors and shamans (Michelot  & Melendez-Howell,  2003; Wasson, 1959; Dugan, 2011; Yamin-Pasternak, 2011 ).

The most important toxins in terms of contamination of human food are the aflatoxins. These toxins are produced by the filamentous Ascomycota Aspergillus flavus and A. parasiticus (and less frequently by several other species of Aspergillus) as secondary metabolites when the fungi grow saprotrophically on stored food products at temperatures between 24 and 35° C, and moisture contents higher than 7% (10% with ventilation). Food products likely to be contaminated with aflatoxins include cereals, such as maize, sorghum, pearl millet, rice, wheat, oilseeds like groundnut (peanut), soybean, sunflower, cottonseeds, spices including chillies, black pepper, coriander, turmeric, and ginger, tree nuts such as almonds, pistachio, walnuts, coconut and pecans. Because the milk of animals fed on contaminated crops can also contain high concentrations of aflatoxin, dairy products from farm animals can also be contaminated.

The contamination occurs when the mould fungus grows on the crop and secretes the aflatoxin, either through its growth in the field or during post-harvest storage. According to FAO estimates, 25% of world food crops are affected by aflatoxins each year (Moretti et al., 2017; Dövényi-Nagy et al., 2020).

In well-developed countries, aflatoxin contamination rarely occurs in foods at levels that cause acute aflatoxicosis in humans, but Williams et al. (2004) conclude that about 4.5 billion people (that’s about two-thirds of the human population) living in developing countries are chronically exposed to largely uncontrolled amounts of the toxin. Aflatoxin contamination of grain consequently poses a major threat to human and livestock health, and aflatoxin content of the diet is at least associated (and may cause) liver cancer. It is no coincidence that liver disease is a common health problem in areas where aflatoxicosis is rife (Kumar et al., 2016; Umesha et al., 2016; Vettorazzi & López de Cerain, 2016).

So, why is Aspergillus attacking humans with aflatoxins? The truth is, of course, that there is no way that aflatoxin production could have evolved in Aspergillus in the time (maybe a few thousand years) that humans have been developing agriculture to the point where we store large amounts of cereal grains and other crops. The biologically important animals in this story are not humans but rodents. About 40% of mammal species are rodents and they cause billions of dollars in lost crops every year because they collect seed grains into stores in their burrows and nests and have an important role in seed dispersal and in dispersing mycorrhizal fungal spores (Stephens & Rowe, 2020). Rodents first appear in the fossil record towards the end of the Palaeocene epoch, 55 to 65 million years ago, and that’s plenty of time for Aspergillus to start competing with the rodents for ‘ownership’ of their grain stores by producing highly toxic feeding deterrents!   

Humans and furry little mammals are not the only animals that eat fungi (see the section on Fungi in food webs in Chapter 11; CLICK HERE to view the page) (Singh et al., 2014), and many toxic secondary metabolites are targeted at invertebrates. For example Seephonkai et al. (2004) describe a glycoside from the insect pathogenic fungus Verticillium that is cytotoxic toward animal cells. And in a different type of investigation, Nakamori & Suzuki (2007) show that the cystidia of fruit bodies of Russula bella and Strobilurus ohshimae defend the fruit body against Collembola, producing (unknown) compounds that kill arthropods on contact.

Similar to these compounds are the HMG-CoA reductase inhibitors that were isolated from Pythium and Penicillium cultures in the 1970s by researchers who:

' …hoped that certain microorganisms would produce such compounds as a weapon in the fight against other microbes that required sterols or other isoprenoids for growth...' (Endo, 1992).

The compounds that were isolated became known as the statins; mevastatin, lovastatin, simvastatin, and pravastatin, now marketed around the world as effective and safe cholesterol-lowering drugs that are probably the most widely used pharmaceuticals at the moment. Note that quotation: 'as a weapon in the fight against other microbes'; these compounds are obviously toxic to their target competing species but clearly beneficial to humans. What constitutes a fungal toxin is a matter of definition.

And then there are the strobilurins. Fungi that produce strobilurins (and the related oudemansins) are found all over the world in all climate zones, and with only one exception (Bolinea lutea, an ascomycete) all belong to the Basidiomycota. Strobilurins and oudemansins inhibit the mitochondrial respiratory chain of fungi by binding to the ubiquinone (= coenzyme Q) carrier that carries electrons to the cytochrome b-c1 complex (described in the section The endomembrane systems of Chapter 5; CLICK HERE to view the page; CLICK HERE to view the Virtual Cell Animation describing the Mitochondrial Electron Transport Chain).

Fungi that produce strobilurins have a modified amino acid sequence in the binding envelope of the coenzyme Q protein that greatly reduces its binding affinity for strobilurin, and make the strobilurin-producer strobilurin-resistant.

At present there are about eight synthetic strobilurins in the fungicides worldwide market that are used against a range of fungal diseases in various agricultural crops. Strobilurins now hold an approximate 20% share of the world fungicide market (Balba, 2007). This entire market is based on fungal toxins that are toxic to other fungi but have what is described as ‘outstanding environmental tolerability’ meaning that they have negligible effects on all other organisms.

One final facet of the fungal toxins story is their potential as weapons; either the biological component (the fungus) or the specific chemical component (the active toxin itself).  Paterson (2006) argues that the low molecular weight toxins rather than the fungi themselves are the biggest threat as bioweapons. Although none are yet known, or even suspected, to have been ‘weaponised’, it is necessary to be aware of the potential threats so that treatment and decontamination regimes can be developed in advance. As with most threats, it’s better to be prepared than paranoid (Zhang et al., 2014).

Updated January, 2021