Reversing Natural Selection

Antibiotic drugs are a well-known test of the idea of natural selection. By killing sensitive bugs, they leave more space and nutrients for resistant ones to thrive. Genes for resistance thus spread through the population unless such drugs are used carefully and sparingly. However, as with other sorts of drug, different types of antibiotic may interact with one another in unexpected ways. 

In a paper published in a recent issue of Nature, and highlighted in The Economist, Roy Kishony and his team from Harvard University have just shown that one such interaction has the paradoxical effect, giving the advantage to drug-sensitive bacteria instead of drug-resistant ones. 

Dr. Kishony’s team studied two strains of E. coli. One of these strains was sensitive to doxycycline, the other was doxycycline-resistant. When the two were grown in cultures containing doxycycline, the resistant strain, as expected, did better. However, when the researchers grew each strain in cultures containing both doxycycline and a second antibiotic, ciprofloxacin, they found the opposite effect. This time it was the doxycycline-sensitive strain that did better even though, in principle, it was not resistant to either drug. 

The real test came when Dr. Kishony pitched the two strain against each other. He labelled the doxycycline-resistant strain with a yellow protein and the sensitive with a blue protein. When only doxycycline was added to the mixture, the yellow team prevailed. But when both drugs were present, blue bacteria swept the field – or rather, the Petri dish. When faced with a two-pronged attack, therefore, it was the drug-sensitive strain that had the selective advantage. 

Exactly how the two drugs interact to produce this result is not yet clear. They work in different ways. Doxycycline gums up the assembly line on which proteins are made, whereas ciprofloxacin stops the DNA message about how to make each protein being read in the first place, so there is plenty of scope for interference between the two. 

Whether Dr. Kishony’s discovery has any clinical implications remains to be seen. As he observes, the experiments were performed on bacteria that live in the laboratory under highly controlled conditions. Nevertheless, this study opens a novel way of looking at the problem of resistance. Using one drug to neutralize resistance to another looks worthy of further research.