Dr Cédric Laguri - Bacterial cell wall recognition and biosynthesis through integrated structural biology

Dr Cédric Laguri - Bacterial cell wall recognition and biosynthesis through integrated structural biology

Cédric Laguri
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IBS Grenoble

Bacterial cell wall recognition and biosynthesis through integrated structural biology

Bacterial lipopolysaccharides (LPS) are key determinants of Gram-negative cell envelope integrity and play a central role in host–pathogen interactions. While their structural diversity underlies immune evasion and adaptation, specific recognition by host receptors remains a critical step in innate immunity. In particular, C-type lectin receptors (CLRs) have emerged as important mediators of LPS sensing through glycan-dependent interactions. Here, we use integrated structural biology approaches to dissect the molecular basis of LPS recognition by C-type lectins. Our work reveals how variations in LPS influence binding specificity and affinity, and the importance of lectin arrangement and glycan presentation. Beyond recognition by the immune system, we also investigate several cell wall glycoconjugates biosynthetic machineries, with the prospect of identifying new targets for antibiotic development (1–4).

Selected references

(1) Abbas, M.; Micciulla, S.; Teulon, J.-M.; Maalej, M.; Trembley, M.; Marchetti, R.; Molinaro, A.; Thépaut, M.; Fieschi, F.; Pellequer, J.-L.; Laguri, C. Lipopolysaccharide Nanoparticles: A Biomimetic Platform to Study Bacterial Surface. Biophys. J. 2025. https://doi.org/10.1016/J.BPJ.2025.06.036.
(2) Nieto-Fabregat, F.; Marseglia, A.; Thépaut, M.; Kleman, J.-P.; Abbas, M.; Le Roy, A.; Ebel, C.; Maalej, M.; Simorre, J.-P.; Laguri, C.; Molinaro, A.; Silipo, A.; Fieschi, F.; Marchetti, R. Molecular Recognition of Escherichia coli R1-Type Core Lipooligosaccharide by DC-SIGN. iScience 2024, 27 (2), 108792. https://doi.org/10.1016/j.isci.2024.108792.
(3) Abbas, M.; Maalej, M.; Nieto-Fabregat, F.; Thépaut, M.; Kleman, J.-P.; Ayala, I.; Molinaro, A.; Simorre, J.-P.; Marchetti, R.; Fieschi, F.; Laguri, C. The Unique Three-Dimensional Arrangement of Macrophage Galactose Lectin Enables E. Coli LipoPolySaccharides Recognition through Two Distinct Interfaces. PNAS Nexus 2023. https://doi.org/10.1093/pnasnexus/pgad310.
(4) Baeta, T.; Giandoreggio-Barranco, K.; Ayala, I.; Moura, E. C. C. M.; Sperandeo, P.; Polissi, A.; Simorre, J.-P.; Laguri, C. The Lipopolysaccharide-Transporter Complex LptB2FG Also Displays Adenylate Kinase Activity in Vitro Dependent on the Binding Partners LptC/LptA. J. Biol. Chem. 2021, 297 (6), 101313. https://doi.org/10.1016/j.jbc.2021.101313.