Better understanding the defence system of bacteria to better attack them

Jean-François Collet, a researcher at the Duve Institute at UCLouvain, and his team have been studying bacterial resistance to antibiotics for over 20 years. His latest discovery? His laboratory has demonstrated that the defence mechanism of bacteria, long attributed to a single layer, is in fact based on the cooperation of the three layers that make up their envelope. ‘This is one of my laboratory's most significant contributions,’ says Jean-François Collet enthusiastically. Why is this interesting? "This discovery, published in the prestigious scientific journal Nature Microbiology, will revolutionise the way scientists have understood certain defence mechanisms against antibiotics until now.

In concrete terms, when a bacterium is attacked (e.g. by an antibiotic), it implodes. To resist these attacks, bacteria build fortifications with several lines of defence. One of these lines of defence, called peptidoglycan, forms a rigid structure, a kind of extracellular skeleton.

Until recently, the consensus was that peptidoglycan, a kind of rigid wall surrounding the bacterium, was sufficient on its own to resist environmental attacks. Like a skeleton maintaining the integrity of a body, peptidoglycan was considered the essential layer preventing the implosion of bacteria, particularly when attacked by antibiotics.

However, scientists at UCLouvain have recently discovered that this consensus, which has been widely accepted for decades, was not entirely correct. Peptidoglycan is certainly important, but it does not have the function that has been attributed to it until now. Jean-François Collet and his team observed that it is part of a broader mechanism involving the three layers of defence, and that it is the entire system that protects bacteria from many antibiotics. This mechanism applies to half of all bacteria known today.

What is the significance of this discovery? Understanding how the three layers work together represents a major paradigm shift that revolutionises our understanding of bacterial defence mechanisms. This breakthrough will enable scientists around the world to gain new insights into bacterial defence and develop new antibiotics that disrupt the bacterial envelope. According to Jean-François Collet, ‘the better we know our enemies (in this case, bacteria) and their means of defence, the better we can attack them or thwart their defence systems.’

Article describing this research

Peptidoglycan-outer membrane attachment generates periplasmic pressure to prevent lysis in Gram-negative bacteria

Deghelt M, Cho SH, Sun J, Govers SK, Janssens A, Dachsbeck AV, Remaut HK, Huang KC, Collet JF

Nat Microbiol 2025,10(8):1963-1974

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LeJournalduMédecin - Antibiorésistance: une défense bactérienne à trois niveaux - 22/08/2025