Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [57]
But an evolutionary biologist named Graham Bell at McGill University in Montreal suspected that E. coli—and its evolutionary potential—might be more powerful than others had thought. Michael Zasloff, for one, didn’t think so. But as a good scientist, he was willing to put his hypothesis to the test. He teamed up with Bell and Bell’s student Gabriel Perron to run an experiment. Remarkably, his hypothesis failed.
The researchers began by exposing E. coli to very low levels of an antimicrobial peptide. A few microbes survived, which the scientists used to start a new colony. They then exposed the descendants of the survivors to a slightly higher concentration of the antimicrobial peptide. Again most of the bacteria died, and they repeated the cycle, raising the concentration of the drug even higher. E. coli turned out to have a remarkable capacity to evolve. After only six hundred generations, thirty out of thirty-two colonies had done the impossible: they had become resistant to a full dose of antimicrobial peptides. These results raise some serious concerns about how effective antimicrobial peptides will be when they hit the market. E. coli and other bacteria that are hit by low doses of antimicrobial peptides may evolve resistance. If they do, they will survive stronger and stronger doses until they can withstand the full strength of these drugs.
If E. coli can evolve resistance to antimicrobial peptides so quickly, then how did they protect Zasloff’s dirty frogs? E. coli and other bacteria are locked in an evolutionary race with the animals they colonize. When an animal evolves a new antimicrobial peptide, natural selection favors microbes that can resist it. One common counterstrategy is for a microbe to make an enzyme that can cut the new peptide into pieces before it is able to do any damage.
Now the evolutionary pressure shifts back to the animal. Mutations that allow an animal to block the peptide-cutting enzyme may allow it to survive infections. It will pass down the mutation to its descendants. Animals defend against peptide-slicing enzymes by stiffening the peptides. The peptides are folded over on themselves and linked together with extra bonds. But microbes have evolved counterstrategies of their own. For example, some species secrete proteins that grab the antimicrobial peptides and prevent them from entering the bacteria.
One of the most potent ways for animals to overcome all of these strategies is by making lots of different kinds of antimicrobial peptides. New ones can be produced by gene duplication or by borrowing peptides with other functions. The more antimicrobial peptides an animal makes, the harder it is for bacteria to recognize them all. Thanks to this arms race, the genes for antimicrobial peptides have undergone more evolutionary change than any other group of genes found in all mammals.
Compared with this complex, ever-changing attack on antimicrobial peptides, Bell and Zasloff’s experiment is child’s play. They exposed E. coli to a single kind of antimicrobial peptide and created a strong advantage for mutants that could withstand it. Unfortunately, modern medicine works more like Bell and Zasloff’s experiment than like our own evolution. Doctors have only a few antibiotics to choose from when fighting an infection, and they generally prescribe only a single drug to a patient. In a few years this practice gives us resistant bacteria. We might do a better job of fighting bacteria if new drugs came through the development pipeline faster and if doctors could safely prescribe several of them at once.
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