Uncovering bacterial pseudaminylation with pan-specific antibody tools
Year: 2025
Type: preprint
Abstract: Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins that are critical for the virulence of human pathogens. However, a dearth of effective tools for detecting and enriching Pse has restricted study to only the most abundant Pse-containing glycoconjugates. Here, we devise a synthesis of α- and β-O-pseudaminylated glycopeptides to generate ‘pan-specific’ monoclonal antibodies (mAbs) that recognise α- and β-configured Pse and its C8 epimer (8ePse) presented within glycans or directly linked to polypeptide backbones. Structural characterisation reveals the molecular basis of Pse recognition across a range of diverse chemical contexts. Using these mAbs, we establish a glycoproteomic platform to provide unprecedented depth in mapping the Pse glycome of Helicobacter pylori , Campylobacter jejuni , and Acinetobacter baumannii strains. Finally, we demonstrate that the mAbs recognise diverse capsule types in multidrug-resistant Acinetobacter baumannii and enhance phagocytosis to eliminate infections in mice.
Authors: Kristian I. Karlic, Arthur H. Tang, Niccolay Madiedo Soler, Leo Corcilius, Christopher Lehmann, Aleksandra Debowski, Ashleigh L. Dale, Lauren Zavan, Michelle Cielesh, Adedunmola P. Adewale, Karen D. Moulton, Lucy Li, Chenzheng Guan, Maria Kaparakis-Liaskos, Benjamin P. Howden, Ruohan Wei, Xuechen Li, Danielle H. Dube, Stuart J. Cordwell, Mark Larance, Keith A. Stubbs, Glen P. Carter, Nichollas E. Scott, Ethan D. Goddard-Borger, Richard J. Payne
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: Defining the roles of O-linked glycosylation on Burkholderia virulence, Characterising O-linked glycosylation across Burkholderia, A multi-pronged approach for the development of effective and safe anticoagulants, Deciphering Helicobacter pylori's glycocode: uncovering and harnessing drug targets, Glycosylation as a new target in myelofibrosis, Repurposing and re-optimising drugs that disrupt glycoprotein folding to treat COVID-19, How does glycosylation shape protein function within Burkholderia?
OpenAlex ID: W4412379526