The discovery of antibiotics is one of the most important breakthroughs of the 20th century. But their effectiveness and low cost has led to their overuse, resulting in the worrying rise of antibiotic-resistant bacteria, or so-called superbugs. Researchers at the University of East Anglia (UAE) in England have now uncovered an Achille's heel in the bacterial cell defenses that could mean that bacteria wouldn't develop drug-resistance in the first place.

The World Health Organization's (WHO's) first global report on antibiotic resistance released earlier this year calls antibiotic resistance a serious threat that is "no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country."

While we've seen other efforts to develop new ways to fight these superbugs, including antibiotic drug "smart bombs" that target specific strains of bacteria, "ninja polymers" based on semiconductor technology, and cold plasma therapy, UAE researchers have discovered a weakness that opens up the possibility of developing drugs that don't attack the bacteria itself, but target the defensive barrier that surrounds its cells.

Up until now, very little was known about how the outer membrane, which surrounds the drug-resistant bacterial cells and protects against attacks from the human immune system and antibiotic drugs, is built. But by examining a class of bacteria called "Gram-negative bacteria," which has an impermeable lipid-based outer membrane that makes it particularly resistant to antibiotics, the researchers found how lipopolysaccharides – the building blocks of this defensive barrier – are transported to the outer surface.

"We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface," said Professor Changjiang Dong, from UEA’s Norwich Medical School and leader of the research group. "Importantly, we have demonstrated that the bacteria would die if the gate is locked."

"The really exciting thing about this research is that new drugs will specifically target the protective barrier around the bacteria, rather than the bacteria itself," added PhD student Haohao Dong, who was the lead author of the study. "Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future."

If the research does indeed lead to the development of a new class of drugs that could effectively kill drug-resistant bacteria, it could be as groundbreaking and prove as important to human health as the development of antibiotics.

The UAE team's research is published in the journal Nature.