I ran across this information the other day. It kind of shocked me- I guess I was not paying attention in my microbiology class. Actually, not- I checked my texts and found no mention in the index. You see, in 1954, Francois Jacob (Institut Pasteur, Paris) described a “pyocin”, a chemical exuded by a strain of microbes (Pseudomonas pyocyanea, now called Pseudomonas aeruginosa) that killed another species of P. aeruginosa. When examined under the electron microscope, these pyocins were found to resemble a rocket- the ones they show in cartoons- one thick tube with several fibers protruding out of its end. It turns out the thick tube also contains a thinner one, that gets expelled by the outer tube (via contraction) to inject itself into the cell wall of the target cell. Killing it.
It turns out that other microbes have these killer rockets. Serratia entomophila uses it to kill beetle larvae. Only one species (New Zealand grass grub) . But, these microbes kill via a toxin within the thin sheath- one that causes the grub to cease eating, starving it, so that the bacteria can devour its tissues, as the insect weakens. Some cholera bacteria are capable of killing mice and amoebae in the same fashion.
The other part of the story? Once the microbe makes this rocket, it is “spent”. It dies. Saving the rest of the species from attack? Yes, these microbes turn out to be part of a social network, where some microbes die to preserve the others.
If you’ve paid attention so far, you might recognize that this process is similar to what bacteriophage use. These viri have a head (called a capsid), surrounding their genetic materials. Attached to the head is a tube with “prongs”, grabbing onto specific bacteria (they are specific, almost every bacteria has its own nemesis phage), and injecting the phage genes into the microbe, which becomes a slave to the phage. The slave microbe makes myriad copies of the gene, until it explodes and yields new bacteriophage progeny. And, yes, the R-type pyocin is very similar to the bacteriophage- without the capsid. There are other types of pyocins that resemble capsid-less lambda phages.
Given this information, AvidBiotics decided to try to make their own pyocins, using the tail fibers of phages instead of the pyocin tail fibers, rendering those that normally kill Pseudomonas to kill Escherichia coli (E. coli). From there, they began developing more specific targeted E. coli species (O157:H57)- the ones that have been in the news because they lead to “killer diarrhea” in humans, plus strains of Salmonella and Shigella. AvidBiotics is limiting their development to intestinal diseases, so that the immunological response that could result from injection into the body can be avoided.
The problem is that the microbes can develop resistance to these impalers, just like they do when subjected to antibiotics. The resistance seems to be related to the carbohydrate (sugar-like) coating which are used in the engineered impalers; removing this coat may stop the development of this resistance. And, we need to engineer these impalers, because bacteriophage that could kill microbes are not static; they evolve and change their specific targets. We want- no, we need- the specific target to stay the same.
But in nature things are always changing. Maybe the premise is wrong somehow. And maybe our desire to cure, prolong and fix people by non-natural or manufactured means are creating more problems. Has nature evolved to combat natural illnesses or have we killed all that off too?
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Well, I think this is using natural systems, Roberta. Just changing the vehicle of attack. Since, there already are phages that kill certain microbes, rendering that toxin more easily used – and, in particular, used at will- is a pretty nifty little idea to me. I hope they do succeed in engineering these newer carriers.
Roy.