Talmudic Question #43

by Mark Martin

How might the botulism bacillus, Clostridium botulinum, benefit from making botulinum toxin? (This question can be extended to the tetanus bacillus and its toxin, as well as to others.)

Comments

[Melanie Berkmen]

Clostridium is an anaerobe. It hates oxygen, which is always being taken up by a live host. The toxin causes paralysis, that results in death due to paralysis of the pulmonary (lung) muscles. Maybe the toxin is Clostridium's way of getting to use the whole body of the host for food. Without stopping breathing, much more of the body would be off-limits for the bug to grow in due to the toxic high levels of oxygen. Does this make sense?

[Brandt Levitt]

I know that the neurotoxin from botulinum has a very high specificity with the human neural system. This is clearly a case for coevolution. Botulinum likely did not simply evolve this for a different purpose, and given its high level of conservation, it must be important in their life cycle. Given that Botulinum isn't particularly hardy, perhaps this is a way to immobilize the host defenses by increasing the probability of starvation of the host. Certainly, a weakened host would not have such a robust or sustained immune response (especially not over the long period of incubation that botulinum requires). The fact that the toxin is produced by growing (rather than bacteria at a specific threshold concentration) supports the idea that it is important in helping botulinum gain a foothold early in pathogenesis. Just my two cents.

[Norman Radin]

Talmudic Question #43 by Mark Martin is a fine accompaniment to my January 19, 2009 article in the Small Things blog about preventing infections. One of the methods described showed how one could use a multimeric form of a sphingoglycolipid to prevent microbes from binding to the substance in the cell wall of a victim cell. In the Talmudic example, the botulinum organism generates a toxin that binds the microbe to a victim's gangliosides GD1b and/or GT1b amd/or GQ1b (sphingolipids containing ceramide + several molecules of neuraminic acid and other sugars). The binding typically requires a protein in the cell wall to act together with the lipid. Since the toxin is present - at least for a while - in the surface of the microbe, it acts as a glue between the two cells.
The toxin may also act as a free, soluble agent, binding to the victim's surface so that the complex now is able to bind the microbe.
A brief query to PubMed, the free search service that accesses 18,000,000 research papers, will show that the fat globules of milk (esp. goat milk) contain the gangliosides, together with a coating of globule protein, so milk can compete with the victim's cells for binding to the microbe and thus prevent or alleviate the infection.
Norm Radin

[Mark O. Martin]

What is ironic/funny about that last comment is that dermatologists are extremely cautious in how they describe Botox. They don't call it "...a potent neurotoxin isolated from a pathogenic bacterium that is best known for causing the potentially lethal food poisoning commonly termed 'botulism'..," to say the least!

[Judith Schaechter]

I'm thinking it should get a kickback from the cosmetics industry. Does that count?

******
Sure! Anything for a buck!
Elio

[Adrian]

Perhaps following enteric colonization the botulinum toxin functions to paralyze the host's GIT and prevent the bacteria from being flushed out by peristalsis.

[Mike Gray]

A large dead animal is a pretty good growth medium for strict anaerobes, I would think...

From another angle, do clostridial toxins have any effect on other soil microbes? How do they effect worms and insects? Could their toxicity towards animals be secondary to some effect on fungi or protozoa? I don't know if anyone's looked for that kind of thing.

[Mark O. Martin]

It is very nice of Elio and Merry to present this question, which was directed to me by some students in my microbiology class last semester (they were fresh from a neurobiology course). The "knowledge base" out in the Internet may provide some interesting insights.

Certainly, the "benefit" to pathogens of toxins can turn into Kipling style "Just So" tales. But it is a challenge to think how attacking proteins (syntaxin, synaptobrevin, etc) that allow vesicles containing neurotransmitters to fuse with neuromuscular junction plasma membranes actually benefits Citizen Prokaryote.

A relative of Clostridium botulinin plays a related "game" with tetanospasmin.

On my more positive days, I often think of these Talmudic Questions as being very intriguing essay problems for "take home" examinations! We would certainly learn how students think by the way in which they approach these integrative and challenging questions!

I look forward to any thoughts readers might have on the the "ecophysiological role" this most toxin protein (LD50 of 1 ng/kg, from what I have read) might play in the life of C. botulinum.

[Steve Hecht]

So how about- toxin kills ducks providing more organic matter for the grubs that are unaffected by the toxin. More transmission and more vegetative good times for the bacteria.