Antibody Recognition of Different Staphylococcus aureus Wall Teichoic Acid Glycoforms.
Autor: Di Carluccio, Cristina; Soriano Maldonado, Pablo; Berni, Francesca; J. C. de Haas, Carla; Robin Temming, A.; Hendriks, Astrid; Ali, Sara; Molinaro, Antonio; Silipo, Alba; M. van Sorge, Nina; J. van Raaij, Mark; Leiden, Codee; Marchetti, Roberta
Resumen: Wall teichoic acids (WTAs) are glycopolymers decorating
the surface of Gram-positive bacteria and potential targets for antibodymediated
treatments against Staphylococcus aureus, including methicillinresistant
(MRSA) strains. Through a combination of glycan microarray,
synthetic chemistry, crystallography, NMR, and computational studies, we
unraveled the molecular and structural details of fully defined synthetic
WTA fragments recognized by previously described monoclonal antibodies
(mAbs 4461 and 4497). Our results unveiled the structural
requirements for the discriminatory recognition of α- and β-GlcNAcmodified
WTA glycoforms by the complementarity-determining regions
(CDRs) of the heavy and light chains of the mAbs. Both mAbs interacted
not only with the sugar moiety but also with the phosphate groups as well
as residues in the ribitol phosphate (RboP) units of the WTA backbone, highlighting their significant role in ligand specificity. Using
elongated WTA fragments, containing two sugar modifications, we also demonstrated that the internal carbohydrate moiety of α-
GlcNAc-modified WTA is preferentially accommodated in the binding pocket of mAb 4461 with respect to the terminal moiety. Our
results also explained the recently documented cross-reactivity of mAb 4497 for β-1,3/β-1,4-GlcNAc-modified WTA, revealing that
the flexibility of the RboP backbone is crucial to allow positioning of both glycans in the antibody binding pocket.
Identificador universal: https://hdl.handle.net/10641/3590
Fecha: 2022
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