28-10-2025
A team of researchers from the Research Unit on Applied Biomolecular Sciences (UCIBIO) at the NOVA School of Science and Technology | NOVA FCT played a central role in discovering a new mechanism that explains how certain microorganisms can adhere to mucus — the viscous substance that protects the inner surfaces of the human body, such as the intestines, lungs, or reproductive tract.
The study, published in the scientific journal Nature Communications (Nature Group), reveals that a small protein from the enterohemorrhagic Escherichia coli bacterium, named X409, acts as a highly specialized “molecular hook” that recognizes specific clusters of sugars — or “sugar patches” — present in mucus. This is the first time that such a recognition mechanism has been demonstrated, based on structural data, as a microbial adhesion strategy.
Understanding how this “molecular hook” works could pave the way for the development of antimicrobial therapies capable of preventing pathogenic bacteria from attaching to mucus, thus avoiding infections, as well as for the creation of more effective probiotics or the improvement of targeted drug delivery.
“To unravel this mechanism, our team combined several cutting-edge structural biology techniques, including nuclear magnetic resonance (NMR), X-ray crystallography, and molecular dynamics simulations. We played a central role in characterizing the interaction between the X409 protein and mucin sugars,” explains Filipa Marcelo, leader of the UCIBIO team.
Mucus is an essential protective barrier of the human body, composed of mucins densely decorated with chains of sugars (glycans). These structures not only defend tissues against pathogens but also nourish and regulate the microbiota — the community of beneficial microorganisms that live with us in symbiosis. Understanding how microbes bind to mucins is crucial to comprehend how beneficial bacteria colonize the human body and how pathogens may exploit mucus to invade tissues.
The work involved PhD student Cátia O. Soares, postdoctoral researcher Ana Sofia Grosso, and contributions from researcher Helena Coelho, and researcher Jorge S. Dias. The NMR experiments and part of the molecular dynamics simulations were carried out at UCIBIO facilities.
The study resulted from a collaboration between the Copenhagen Center for Glycomics (University of Copenhagen, Denmark), BIFI (University of Zaragoza, Spain), IQUR (University of La Rioja, Spain), and UCIBIO – NOVA FCT, one of the three research units of the Associated Laboratory Institute for Health and Bioeconomy (i4HB) in Portugal.
The full article is available in open access at Nature Communications.
