Researchers from the (Bio)molecular Structure and Interactions by NMR Lab at UCIBIO – NOVA FCT played a central role in uncovering a novel molecular mechanism explaining how certain microorganisms adhere to mucus - the viscous substance that protects internal surfaces of the human body, such as the intestines, lungs, and reproductive tract.
The study, published in Nature Communications, identifies a small protein from the bacterium enterohaemorrhagic Escherichia coli, named X409, that functions as a highly specialised “molecular hook” capable of recognising and binding to specific clusters of sugars, or “saccharide patches,” present in mucus. This represents the first structural evidence of such a sugar-recognition strategy being used for microbial adhesion.
“To unravel this mechanism, our team combined several advanced structural biology techniques, including nuclear magnetic resonance (NMR), X-ray crystallography, and molecular dynamics simulations. We played a key role in characterizing the interaction between the X409 protein and mucin sugars”, explains Filipa Marcelo, leader of the UCIBIO team.
Mucus is a critical protective barrier, composed of densely glycosylated mucins that not only defend tissues against pathogens but also nourish and regulate the microbiota – the beneficial microorganisms living in symbiosis with the human body. Understanding how microbes bind to mucins is essential to comprehend how beneficial bacteria colonize the body and how pathogens exploit mucus to invade tissues.
This discovery could lead to the development of antimicrobial therapies that prevent pathogenic bacteria from adhering to mucus, more effective probiotics, and innovative strategies for targeted drug delivery.
The UCIBIO team included doctoral researcher Cátia O. Soares, postdoctoral researcher Ana Sofia Grosso, researchers Helena Coelho, Jorge S. Dias and Filipa Marcelo. The NMR experiments and part of the molecular dynamic simulations were conducted at UCIBIO facilities.
This 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 (NOVA University Lisbon, Portugal), one of the three research units of the Associated Laboratory Institute for Health and Bioeconomy (i4HB).
This paper, entitled “Microbial binding module employs sophisticated clustered saccharide patches to selectively adhere to mucins,” is available in Open Access in Nature Communications.
DOI: https://doi.org/10.1038/s41467-025-63756-w
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