I know… pufferfish!
Pufferfish are tropical fish found especially in Asia. They are called pufferfish because they have a rather unusual defence strategy; they can fill their stomachs with water so that they balloon up into a ball shooting numerous spiky spines outwards. Any predator stupid enough to try and eat a pufferfish gets a mouth or stomach full of spines and probably chokes… nasty. Bloat, from the Disney film “Finding Nemo” was a pufferfish; he blows up like a beach ball every time something startles him… he’s my favourite character and he’s hilarious!
In fact TTX is one of the most potent neurotoxins we know of, being 1200x more toxic than cyanide. It blocks sodium channels in muscles and nerves causing paralysis and eventually death. Why anyone would want to eat something that could kill them I do not know….! To mitigate the risk only specially trained and licensed chefs are allowed to prepare fugu paying careful attention to avoiding the puffer fish’s liver and ovaries where the highest levels of TTX are.
TTX poisoning has also occurred closer to home with a case in Malaga, Spain, in 2007 due to eating shellfish caught in Portuguese waters and in Greece in 2012 from TTX containing molluscs. Anyone for the plato de mariscos del día? OK so maybe the recent ban on going on holiday due to Covid-19 isn’t such a bad thing after all… okay I’m really reaching here and trying to look on the bright side… my holiday is being canned… the South African government have placed UK residents are on a banned list for entry!
Whoa! Hold on! Isn’t this supposed to be a microbiology blog, not a blog about fish or fancy foods or holidays?! Okay, stick with it, I’ll explain…
What the heck does TTX poisoning have to do with microbiology?
The first published association between pufferfish and TTX was “rediscovered” in 1894; I say rediscovered because the association between pufferfish and its toxic effects was actually described in ancient Egyptian texts as far back as 2500BC.
However research in 1968 also discovered TTX in California in a species of newt; previously it was thought that only the pufferfish “produced” TTX, but when they looked further they actually found TTX “contained” in silt and sediment as well as lots of different animals!
Other animals containing TTX include:
Even though these are all aquatic animals it is very unlikely that the ability to “produce" such a specific toxin has evolved in so many different animals in different locations around the World, so there must be another explanation for the presence of TTX.
This where the microbiology comes in… TTX is actually produced by bacteria!
I did tell you; this is a Microbiology blog, honest…
Like many toxins and chemicals in higher animal species, TTX actually starts in small quantities in organisms at the very bottom of the food chain. As we go higher up the food chain the amount of TTX accumulates and concentrates in complex animals until it reaches levels which are lethal to those who eat these animals, including humans.
The bacteria, that can produce TTX, start life in the silt and sediment which is then eaten by molluscs. These filter feeders remove nutrients and bacteria from the water concentrating the levels of bacteria and hence TTX within their bodies. Then other animals like crabs, octopus and pufferfish eat the molluscs further concentrating the TTX. Us humans then come along and eat delicacies like crab, octopus or pufferfish; getting an unhealthy high dose of TTX and becoming sick… simple!
There have been some really elegant experiments to show that TTX is concentrated in this way in these animals. Firstly, wild caught pufferfish containing TTX lose their TTX if they are kept in a TTX free environment and fed TTX free food. Secondly, if these fish are then put back in a TTX environment and fed food containing TTX then they become full of TTX again. This proves the fish themselves aren’t producing the TTX; they are acquiring it from their food. “You are what you eat!”
What’s the bacteria producing TTX?
Worryingly there isn’t one single species of bacterium that produces TTX. It is thought that the ability to produce TTX has spread between bacterial species by horizontal gene transfer on mobile genetic elements such as plasmids or transposons. This is the way that bacteria normally share genetic material that confers some kind of selective evolutionary advantage, such as antimicrobial resistance, so why not also a toxin gene?
The most important TTX producing bacteria, which are also potential pathogens or colonisers of humans, include (but this list may increase in time):
- Vibrio spp.
- Pseudomonas spp.
- Bacillus spp.
- Aeromonas spp.
- Micrococcus spp.,
- Serratia marcescens
- Acinetobacter spp.
- Streptomyces spp.
- Plesiomonas spp.
As yet, we don’t know what evolutionary advantage TTX gives to the bacterium (other than another mechanism to get rid of the “parasitic human” population maybe…?) but it is likely to provide some benefit due to the energy cost to produce TTX; Mother Nature doesn’t use energy without good reason and certainly doesn’t waste it.
How dose TTX poisoning present?
TTX poisoning is dramatic. The severity of the illness is dependent on the amount of toxin ingested. Symptoms usually begin within 30 minutes of toxin ingestion, although occasionally this can be delayed up to 6 hours. The fastest recorded time from ingestion to death is a scarily fast 17 minutes!! That would mean death before ordering desert… that’s a tragedy… I do like puddings!!
Initial symptoms include tingling of the tongue and lips which then progresses to headache, vomiting and muscle weakness, followed by respiratory and heart failure and then death. Other symptoms and signs include: numbness, abdominal pain, cardiac arrhythmias, hypotension, loss of coordination and cranial nerve palsies. Another scary thing about TTX poisoning is that it doesn’t affect levels of consciousness so the patient is usually conscious while all this is going on.
On the bright side, if someone is going to survive then they usually recover within 24 hours… so at least you don’t have to wait too long before you know your fate.
How is TTX poisoning treated?
Bad news again; there is no antidote or treatment for TTX poisoning. You either live or you die. Supportive care with mechanical ventilation and antiarrhythmic therapies until the patient recovers is all that can really be offered at present.
However, if a patient presents quickly enough (within 1 hour) then flushing out their stomach using gastric lavage and giving them activated charcoal to drink in order to bind the toxin, may reduce the amount of TTX they absorb and hence reduce the severity of their illness.