Atomic-Level Dissection of DC-SIGN Recognition of Bacteroides vulgatus LPS Epitopes

Ferran Nieto-Fabregat; Qian Zhu; Corinne Vivès; Yunqin Zhang; Angela Marseglia; Fabrizio Chiodo; Michel Thépaut; Diksha Rai; Suvarn S Kulkarni; Flaviana Di Lorenzo; Antonio Molinaro; Roberta Marchetti; Franck Fieschi; Guozhi Xiao; Biao Yu; Alba Silipo

doi:10.1021/jacsau.3c00748

Atomic-Level Dissection of DC-SIGN Recognition of Bacteroides vulgatus LPS Epitopes

JACS Au. 2024 Feb 12;4(2):697-712. doi: 10.1021/jacsau.3c00748. eCollection 2024 Feb 26.

Authors

Ferran Nieto-Fabregat¹, Qian Zhu², Corinne Vivès³, Yunqin Zhang⁴, Angela Marseglia¹, Fabrizio Chiodo⁵, Michel Thépaut³, Diksha Rai⁶, Suvarn S Kulkarni⁶, Flaviana Di Lorenzo¹, Antonio Molinaro¹, Roberta Marchetti¹, Franck Fieschi^{3

7}, Guozhi Xiao⁴, Biao Yu², Alba Silipo¹

Affiliations

¹ Department of Chemical Sciences, University of Naples Federico II, Naples 80126, Italy.
² State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
³ Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble 38027, France.
⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650201, China.
⁵ Institute of Biomolecular Chemistry, National Research Council (CNR), Pozzuoli 80078, Italy.
⁶ Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
⁷ Institut Universitaire de France (IUF), Paris 75005, France.

Abstract

The evaluation of Bacteroides vulgatus mpk (BVMPK) lipopolysaccharide (LPS) recognition by DC-SIGN, a key lectin in mediating immune homeostasis, has been here performed. A fine chemical dissection of BVMPK LPS components, attained by synthetic chemistry combined to spectroscopic, biophysical, and computational techniques, allowed to finely map the LPS epitopes recognized by DC-SIGN. Our findings reveal BVMPK's role in immune modulation via DC-SIGN, targeting both the LPS O-antigen and the core oligosaccharide. Furthermore, when framed within medical chemistry or drug design, our results could lead to the development of tailored molecules to benefit the hosts dealing with inflammatory diseases.