What doesn’t kill them makes them stronger

Bacteria threatened by antibiotics respond by slurping up bits of DNA from their surroundings, some of which are likely to make them resistant to the antibiotics. That ought to worry people. It probably won’t, one reason why antibiotic resistance is the problem it is.

Many bacteria respond to some stresses with an SOS response. Essentially a heightened ability to repair damaged DNA, the SOS response can also result in rapid changes in DNA that may enable the bacteria not only to survive the immediate stress, but to weather it better in future. A group led by Jean-Pierre Claverys, of the Laboratoire de Microbiologie et Génetique Moléculaires in Narbonne, France, show in a paper in this week’s Science that Streptococcus pneumoniae, which is responsible for a burden of diseases way beyond pneumonia, has something similar that is possibly even more effective.

DNA damage causes S. pneumoniae to change its behaviour, to become “competent for genetic transformation”. The changes are complex. What they mean is that competent cells can absorb DNA from the environment and incorporate it into their own genomes. That DNA might just confer resistance to the antibiotic that damaged the DNA in the first place. Better yet, competent cells can kill their non-competent neighbours. That frees the non-competent cells’ DNA, which may well contain genes for antibiotic resistance, because they would have no reason to become competent if they were resistant to antibiotic damage.

The upshot is that fratricide and competence together act to generate a mass of genetic diversity, a veritable smorgasbord of genes there for the taking. Some of the genes are likely to confer new abilities on the competent cells that take them up. And that is why Claverys and his colleagues sound a bit of an alarm. S. pneumoniae is relatively common, without causing any symptoms. One study in Sweden found that more than a third of children carried antibiotic resistant strains of the bacteria without showing any symptoms. Susceptible strains are even more common. Give those carriers certain antibiotics -- for other diseases -- and the S. pneumoniae could well pick up additional resistance. As the French team puts it:

[I]nappropirate antibiotic treatments could accelerate the occurrence of additional resistant clones and promote the evolution of virulence.

All of which prompts me to reflect that, as I hinted before, antibiotic resistance is a huge squandered commons. There is no question that pathogens will develop resistance. The only questions are how quickly and how often. And yet patients have demanded them and doctors have prescribed them with little thought for the consequences. In many places the doctor is an unnecessary element in a simple transaction between self-dosing buyer and self-enriching seller. Worse, farmers have strewn the stuff about in search of profits now with no thought of the costs to be paid by the rest of us.

“The world has become a dilute solution of tetracycline,” as Stuart Levy, one of the few people to sound the alarm, told me many years ago.

Not just tetracycline. And the result is massive multiple resistance. Our best weapons have become useless, by being used both too little and too often.

As a footnote, it is fitting that Claverys studied transformation competence in S. pneumoniae. In 1928 Frederick Griffith injected mice with two forms of the bacteria. One was the normal, virulent and lethal form. The other was a mutant that caused no disease. Griffith killed the virulent bacteria by heating them. Mice that received the dead bacteria stayed perfectly healthy. So did mice that received the non-lethal form. But mice that got a mixture of live, safe bacteria and dead dangerous ones died.

Something -- Griffith called it the transforming principle -- made the safe bacteria lethal again. That something turned out to be DNA, and Griffith’s experiment was an absolutely vital step in identifying the chemical basis of heredity.

This is turning into antibiotic resistance week, with one more to come if I can find the time.