Superbugs may be here to stay

Multidrug-resistant bacteria may be here to stay. The common wisdom that superbugs with antibiotic resistance are outcompeted by their non-super neighbours in the absence of antibiotics has been turned on its head.

Bacterial antibiotic resistance is a major concern because it can lead to the appearance of dangerous and difficult-to-treat infections in humans. Resistance generally occurs in one of two ways: either through mutations in the bacterial DNA or, more commonly, through the acquisition of resistant genes from other organisms through horizontal gene transfer.

In both cases, previous studies had found that the superbugs lose their competitive advantage once the antibiotics are no longer present. For instance, a voluntary ban by Danish farmers on the use of antibiotic growth promoters in chicken and pigs cut antibiotic resistance in the bacteria within the animals by over 90 per cent.

This is largely because maintaining a newly acquired chunk of DNA from another organism – or coping with a new mutation that imparts antibiotic resistance – uses up so many of the cell's resources, says Francisco Dionísio at the University of Lisbon, Portugal. That means the superbug cannot compete with non-resistant bacteria once the antibiotic has been removed and the playing field has been levelled.

But now Dionísio and colleagues have found that this is not always the case. The team focused on 10 strains of Escherichia coli bacteria that had already acquired genes for antibiotic resistance from other organisms.

Super superbug

When these bacteria independently evolved one of five DNA mutations also associated with antibiotic resistance, something peculiar happened: in five of the 50 resulting strains the bacteria could outcompete typical non-resistant bacteria when both were grown in a dish, even in the absence of antibiotics.

A similar thing happened when the team began with E. coli that had first acquired resistance to antibiotics through genetic mutation and then gained further resistance by acquisition of a resistance-carrying genetic element from another organism. This time 32 per cent of the superbug strains remained more competitive than the non-resistant bacteria once the antibiotic had been removed.

This kind of process is known as positive epistasis, says Dionísio – but he adds that why two negative impacts on a microbes' fitness should work together to give a positive boost to its survival rate "remains a mystery".

"It was a real surprise to find so many cases where the multi-resistant bacteria were at an advantage," says Isabel Gordo, a member of the team based at the Gulbenkian Science Institute in Oeiras, Portugal. "We suspect that this is very important in maintaining antibiotic resistance at the high levels currently seen."

Jim Caryl, an antibiotic resistance researcher at the University of Leeds, UK, says that the problem could be tackled by always using the antibiotics that have the highest fitness cost to the bacteria. This should reduce the chance of positive epistasis emerging, he says.

Dionísio disagrees: what's really needed is an alternative to antibiotics, he says. "We need drugs which will stop the transfer of genetic elements between bacteria – it's amazing that we still don't have a good way of doing this."