I was sitting at my desk, minding my own business, when I felt a sting on my left knuckle. Expecting to find a bee, I was surprised to find the culprit here was a small colorful beetle about the size of a sesame seed. I pulled it off my hand and tossed it outside. Over the course of a day, however, my hand swelled, itched, and throbbed. Three days later, the swelling and itching remain. I have to salute this little beetle adversary – what a weapon it wields! In homage to this creature and to toxic creatures in general, I will review the diversity of living things that produce poisons and venoms to deter predation and hunt prey. This is a huge topic, of course, so this article will be somewhat general. In future articles, I will drill down into more specifics, because toxins are really a lot of fun to know about!

First to definitions of the two major types of toxins: venoms and poisons. Venoms are injected into the body, and poisons act following ingestion by mouth or absorption through the skin. These toxins can be made by viruses, bacteria, protists, fungi, plants, and animals.

Let’s start with viruses. Viruses are not alive. They are a cluster of chemicals that can hack into a cell and take over, just like computer viruses do, using codes to replicate the virus’s sequences. Some viruses integrate themselves into the host’s DNA so they are carried along – effectively hitching their wagon to a star – so the more the host replicates, the more the virus also replicates. Many bacterial viruses carry a toxin gene, increasing the bacterium’s virulence by killing or debilitating the bacterial host or its immune system [1], such as the bacteria that cause cholera, dysentry, C.diff and scarlet fever. The thankfully rare disease, diphtheria, causes a sufferer to choke slowly to death as cells killed by the potent diphtheria toxin accumulate as a tough membrane in the throat, restricting the flow of air to the lungs. However, the diphtheria bacterium, Corynebacterium diphtheriae, does not make diphtheria toxin. Hitchhiking inside some strains of the bacterium is the deadly virus Phage β, which makes the toxin. Without the virus passenger, infection with Corynebacterium diphtheriae would be an unremarkable event. The inactivated diphtheria toxin has been used in the DPT vaccine that protects against diphtheria, pertussis, and tetanus.

Bacteria are also eye-popping in terms of the toxins they harbor, and most are targeted against niche competitors like other bacteria and fungi. But when directed towards animals, bacterial toxins cause either direct or indirect cell killing. The direct actions are obvious: enter the cells and consume them from the inside or burst them and revel in the food abundance that flows out. Toxins may damage host cell structures like ribosomes and DNA, killing the cell. Pseudomonas aeroginosa, which causes pneumonia, stops the cell’s ribosomes from making proteins, a cellular death sentence. E.coli and Salmonella produce enterotoxins which kill gut cells and cause diarrhea. Some bacteria instead produce toxins that disable either a part, or the whole, of the animal body. Tetanospasmin is a deadly neurotoxin produced by sporulating bacteria of the Clostridium family. Resultant nerve activation causes muscles to stay contracted in response, leading to respiratory arrest and death. A clever indirect action exhibited by some pathogens and their toxins leads to the immune system being compromised, causing the pathogen to slip through, or causing the body to self-destruct. For example, Listeria monocytogenes can be taken up by white blood cells but, once inside, lipid-targeted toxins disable the cell’s ability to digest them. The Listeria then hijack the white blood cell and use it to transport themselves around the body, setting up a systemic infection that can lead to sepsis and death. On the other hand, superantigens produced by Staphylococcus aureus or Streptococcus pyogenes cause systemic inflammation, often leading to death. What is most fascinating is that bacteria can switch on various toxin genes by conducting a nutrient analysis of their surroundings, or by sensing how many other bacteria are present in the invading cohort: a mechanism called quorum sensing. If the numbers are large enough, the bacteria switch on their virulence genes and attack; lacking a quorum, they cloak themselves and hide away from the immune system. If you have nothing else to do when you’re locked down or quarantining, http://www.phidias.us/victors/ is a searchable database of toxin genes of bacteria and viruses. There are over 5,000 characterized genes in this database, but there are many that still are not understood.

Protists are small eukaryotic cells – cells that are not quite animals, plants, or fungi – but are evolutionary precursors of all of these groups. Most of us are familiar with the saying “Do not eat shellfish in months without an “R” in them”. This is because some protists like the “red tide” dinoflagellates produce saxitoxin, that causes paralytic shellfish poisoning (PSP), and brevetoxin, that causes respiratory distress. These protists proliferate in summer months in the warm waters off the Gulf Coast, Florida, and California, and spreading northwards with warming waters due to climate change. Filter-feeders like clams can bioaccumulate these toxins, becoming toxic themselves. It’s a good idea to know where your clams come from!

Moving along, we come to Kingdom Fungi. These are a huge and diverse group but all are dependent, like animals, on “eating” other living or dead things. Inconveniently, most fungi are rooted in place, making them poor predators but easy prey. Therefore they have developed a deadly arsenal that causes potential predators to drop dead instantly and become food for the fungi as they decompose. Many fungi are therefore graced with evocative names such as Death Cap, Deadly Dapperling, and Destroying Angel. Amanita mushrooms produce amatoxins, one of which, alpha-amanitin, is a potent inhibitor of protein synthesis and therefore deadly. Other toxins are muscarines which are similar in action to the nerve gas, Sarin, and inhibit the neurotransmitter acetylcholine; ergot alkaloids are caused by fungal infection of grain and cause hallucinations or restriction of blood supply. Many toxic mushrooms look just like their edible cousins, so only go mushroom foraging if you know how to identify edible mushrooms. As an aside, while not toxic, some fungi are active predators and lie in wait with a hyphal loop to trap and kill nematodes. This provides a source of food to absorb (see https://youtu.be/hWdmL8sGCB4).

I hardly need to discuss poisonous plants; their presence and effects are so well known that their alkaloids and terpene chemical repositories are considered the medicine cabinet of the world. Plants produce toxins in their leaves, their seeds, and their roots for protection against being eaten. Many are active against their greatest nemesis, animals, and thus we get many cell-killing chemicals from plants,  such as taxol from the yew plant and vinblastine from the periwinkle plant, which have been harnessed as chemotherapy agents against cancer. Digitoxin, caffeine, opioids, nicotine, cyanide, oxalic acid, curare…these are all chemicals that plants produce so animals will leave them alone. Alas for the plants – they are now exploited for those very chemicals. Bees collect plant exudates such as resin and sap, in addition to nectar and pollen, as an ingredient for propolis as a sticky trap and to coat the inside of the cells in which larvae grow to keep bacteria and fungi at bay. As for pets and their tendency to chew on things, the ASPCA has produced a list of plants that are toxic to dogs, cats and horses (https://www.aspca.org/pet-care/animal-poison-control/toxic-and-non-toxic-plants).

And now, to toxic animals. Venomous and poisonous animals are commonplace – many spiders, scorpions, insects and snakes pack a nasty punch, but most use their venom as a way to capture prey or to protect themselves. Many of these venoms are injected into the body using teeth or stingers. The venoms are often mixtures and the major components are hemolytics, coagulants, nephrotoxins, hemorrhagins, cytotoxins, neurotoxins, necrotoxins and myotoxins. Bee venom contains apitoxin, a cytotoxin which stimulates local inflammation as well as cell death. Curiously, many animals are resistant to their own venom. Even more curious are the animals that are toxic by virtue of the food they eat. We know about how Monarch butterflies and their larvae accumulate the alkaloids of the milkweed to make themselves unpalatable, but some animals take it to deadly extremes. Take the poison dart frog, also known as the poison arrow frog. Some species of this animal are so deadly that merely touching them can kill you. In truth, this doesn’t really appear to be a great superpower because the Amazonians who discovered this also found that the best way to make the frog ooze this toxin, curare, was to roast it alive over a fire and dip their arrows in the ooze as the frog slowly cooked to death. Hence the poison arrow moniker. Herpetologists who carefully took the frogs out of the wild to zoos found, by accident, that the wild frogs slowly lost their toxicity. It transpires that, in the wild, the frogs eat ants and beetles which feed on toxic plants. The ants and beetles store the toxins in their bodies to deter predators. This may mostly work, but not with the frogs, which suck up the poison and use it to make themselves deadly. Until, of course, they are deprived of their toxic food.

This makes the pithy saying “You are what you eat” more than just idiomatic.

1.           Davies, E.V., et al., The role of temperate bacteriophages in bacterial infection. FEMS microbiology letters, 2016. 363(5).