Bacterial glycoconjugates at the host–microbe interface: how can NMR and computational approaches unlock their secrets?

Bacterial glycoconjugates are central players at the host–microbe interface. Their remarkable structural diversity underlies broad biological functions but also complicates their molecular characterization. This review highlights NMR spectroscopy and computational methods as essential tools to address this complexity. NMR provides atomic-level insights into structural details, conformational dynamics, and binding epitopes. Computational approaches complement these results, predicting conformations, refining interaction models, and linking flexibility to recognition events. Combined with additional biophysical techniques, these strategies enable a multidisciplinary framework for investigating the structure and conformation of bacterial glycoconjugates as well as the molecular basis of their interaction with host receptors. Case studies illustrate how the synergy of experimental and theoretical methods can come to the aid of providing high-resolution models that connect molecular structure with biological functions. Looking ahead, this integrated approach is crucial for disclosing the structural basis of recognition by host proteins, clarifying mechanisms of immune evasion, and defining protective epitopes relevant for vaccine design, thus promising translational applications, including diagnostics, immunotherapy, and the rational design of next-generation antimicrobial strategies.