Scientists have discovered the complex process by which antibiotic resistance allows bacteria to multiply in the presence of drugs.
Many approaches are being employed to limit the spread of antibiotic resistance in bacteria - such as limiting the use of antibiotics in livestock, controlling prescriptions of antibiotics and developing new drugs against bacteria already resistant to conventional drug treatments.
"Understanding how bacteria harbouring antibiotic resistance grow in the presence of antibiotics is critical for predicting the spread and evolution of drug resistance," scientists from the University of California, San Diego said.
Researchers found that the expression of antibiotic resistance genes in strains of the model bacterium E coli depends on a complex relationship between the bacterial colony's growth status and the effectiveness of the resistance mechanism.
"In the course of developing complete resistance to a drug, a strain of bacteria often first acquires a mechanism with very limited efficacy," said Terry Hwa, a professor of physics and biology who headed the research effort.
The interaction between drug and drug-resistance is complex because the degree of drug resistance expressed in a bacterium depends on its state of growth, which in turn depends on the efficacy of drug, with the latter depending on the expression of drug resistance itself, according to Hwa.
For a class of common drugs, researchers realised that this chain of circular relations acted effectively to promote the efficacy of drug resistance for an intermediate range of drug doses.
In their experiments, E coli cells possessing varying degrees of resistance to an antibiotic were grown in carefully controlled environments kept at different drug doses in "microfluidic" devices.
Researchers found a range of drug doses for which genetically identical bacterial cells exhibited drastically different behaviours: while a substantial fraction of cells stopped growing despite carrying the resistance gene, other cells continued to grow at a high rate.
This phenomenon, called "growth bi-stability," occurred as quantitatively predicted by the researchers' mathematical models, in terms of both the dependence on the drug dose, which is set by the environment, and on the degree of drug resistance a strain possesses, which is set by the genetic makeup of the strain and is subject to change during evolution.
"Exposing this behaviour generates insight into the evolution of drug resistance. With this model we can chart how resistance is picked up and evaluate quantitatively the efficacy of a drug," said Hwa.
The article was published in the journal Science.
