Degradation Is Good-When Thinking About Antibiotic Resistance

Microbiologist Julian Davies once said that the world is bathed in a dilute solution of tetracycline (an antibiotic). Between human use and production in the environment by naturally-occurring bacteria, there’s a lot of tetracycline out there. In spite of all of this tetracycline, most soil bacteria, and even a fair number of clinical bacteria are sensitive to tetracycline. This led researchers to examine in a 2010 paper (pdf) if tetracycline resistance is disadvantageous in certain habitats.
Before getting to the paper, it’s worth reviewing some elementary basics of antibiotic resistance. Resistance that arises spontaneously via point mutations–changes in the smallest subunit of DNA–often imposes a cost: the bacteria grow slower. Why the slower growth? Antibiotics target critical systems in the cell, such as protein manufacture. Changes in these targets often impair these important function, even as they allow the bacterium to survive. But in the absence of antibiotics, they grow much slower than sensitive bacteria.
But there’s another type of resistance–and this is the most common type observed in the hospital*–known as inducible resistance. Typically, there is a new gene that the cell has acquired**, and which is only turned on when the antibiotic is present. Thus, no vital systems are damaged (although there can still be some costs) and the cell also doesn’t waste resources producing a protective system when it doesn’t need it.
So, with this wonderful low-cost system, why don’t most or all bacteria carry around tetracycline resistance?

The answer has to do with the degradation of tetracycline. When tetracycline isn’t kept stable (e.g., cool), some of the tetracycline breaks down and forms new chemical compounds (this is why some antibiotics need to be kept in the refrigerator). These compounds, while unable to kill bacteria, fool the bacterium into inducing tetracycline resistance. This is actually costly, such that, in the presence of degraded tetracycline, tetracycline sensitivity is favored. While the particular outcomes will depend on the amount of tetracycline and how quickly it degrades, this is an intruiging mechanism.
It would be interesting to see how this plays out in a structured habitat, as the degradation products should be preferentially located at the outer boundaries of the ‘tetracycline zone.’
Cited article: Palmer AC, Angelino E, Kishony R. 2010. Chemical decay of an antibiotic inverts selection for resistance. Nat Chem Biol. 2010 Feb;6(2):105-7.

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