BioEd Online

Chemists have worked out how to return drug-resistant bacteria to their original, susceptible state.

They have identified a molecule that forces microbes to give up the DNA that confers drug resistance and suggest that the same principle could be used to develop treatment for infected patients.

Bacteria often develop resistance to antibiotics by, for example, mutating the part of them that the drug is targeting or gaining the gene for an enzyme to neutralize the drug. Whereas treatment kills off most of the cells, any resistant organisms quickly flourish and become dominant.

The most common way for resistance genes to spread is on small loops of DNA called plasmids, which are separate from the organism's genome and can spread quickly from one cell to another.

Because the majority of useful antibiotics are variations on just three ways of killing bacteria, a plasmid containing one or more resistance genes can render a whole class of drugs useless.

Pitching out plasmids

Paul Hergenrother, a chemist at the University of Illinois, Urbana-Champaign, has found a way to evict plasmids from antibiotic-resistant bacteria, leaving the microbes open to attack from conventional drugs.

His team used a molecule called apramycin, which mimics a short section of RNA. This molecule interrupts the plasmid's replication by sticking to RNA strands that carry its genetic information. This 'blocks' the strands, at which point the host bacterium categorizes the plasmid as a foreign body and ejects it. Although this is a well-known effect, scientists do not really understand why it happens, explains Shahriar Mobashery, a chemist from the University of Notre Dame in Indiana.

The team tested its chemical weapon on Escherichia coli bacteria that harboured a plasmid that made them resistant to the antibiotic ampicillin.

The researchers found that the bacteria lost their protective plasmid and were quickly killed off by ampicillin. The results are published online in the Journal of the American Chemical Society¹.

The tactic could eventually give doctors a vital weapon against the superbugs, says Mobashery. "As far as I know, it's entirely novel," he told news@nature.com.

Apramycin is not likely to be used in clinical trials, because it is quite toxic. But now that the chemists have proved how it works, they are looking for other molecules that could do the same job without causing problems for the patient.