Scientists at UCLouvain have discovered that the three distinct layers of bacterial cell envelopes work together to protect against threats, challenging the long-held belief that only one layer played a dominant role.
The study, published in Nature Microbiology, overturns the conventional model that viewed peptidoglycan—a rigid, wall-like structure surrounding bacteria—as solely responsible for resisting external attacks, including antibiotics.
According to the researchers, this breakthrough offers fresh perspectives on bacterial defences and could pave the way for designing new antibiotics.
"Until recently, peptidoglycan was considered the key layer preventing bacterial implosion," explained Jean-François Collet, a professor at UCLouvain’s Duve Institute.
However, his team has shown that this "extracellular skeleton" is part of a broader defence system involving all three envelope layers.
"It’s the entire system, not just a single layer, that protects bacteria from many antibiotics," he noted. This mechanism is relevant to about half of known bacteria, including Escherichia coli and Salmonella.
The researchers describe their findings as "a major paradigm shift" that could inspire the development of new antibiotics targeting the bacterial envelope as a whole. “The better we understand our adversaries and their defence strategies, the more effectively we can counter them,” Collet emphasised.
This discovery comes at a critical time, as antibiotic resistance is becoming an increasingly urgent global health challenge. The World Health Organisation (WHO) already recognises antimicrobial resistance as a “major” threat to global health.
"As bacteria grow ever more resistant, it’s not unreasonable to imagine that in 15 to 20 years, we may face a situation similar to the pre-penicillin era of the early 20th century," warned Collet.
This groundbreaking research underlines the need for innovation in combating antibiotic resistance, offering hope in a pivotal fight for modern medicine.

