For over a century, scientists have studied E. coli, one of the bacteria that cause food poisoning, as a model for fighting infections. Such research has led to a variety of antibiotics that penetrate the protective cell walls of bacteria to kill them.

Now, a multi-university study overseen by KC Huang, PhD, associate professor of bioengineering and of microbiology and immunology at Stanford, reveals that E. coli has managed to keep a big secret about its defenses.

He and his collaborators report in a paper published in Nature that scientists had overlooked the astonishing physical strength of the thin outer membrane that clings to E. coli’s stout cell wall. Huang is the senior author of the study. The lead author is former postdoctoral scholar Enrique Rojas, PhD.

Scientists have long known that many bacteria have an outer membrane. But until now, they thought of it as a layer of shrink wrap that simply made it tougher to get antibiotics into cells. But as the new study shows, the outer membrane physically protects the cell and could be a good target for a new class of antibacterial drugs.

“We’ve discovered that the outer membrane can act as a suit of armor that is actually stronger than the cell wall,” Huang said. “It’s humbling to think that this function had been hiding in plain sight for all these years.”

Huang said the findings suggest new infection-fighting strategies for the roughly half of all bacterial species that, like E. coli, have outer membranes. “If we can attack the outer membrane, infectious bacteria will be pre-weakened for targeting with antibiotic treatments that disrupt cells in other ways,” he said.