Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: melioidosis [ICD11:
1C42 
, ICD11:
XN3LD 
];
infection due to Burkholderia pseudomallei [ICD11:
XN3LD 
]
NCBI PubMed ID: 26198038Publication DOI: 10.1021/acschembio.5b00502Journal NLM ID: 101282906Publisher: Washington, DC: American Chemical Society
Correspondence: silipo

unina.it
Institutions: Department of Chemical Sciences, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126, Naples, Italy, Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, Nevada 89557, United States, Université de Poitiers, Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, 4 rue Michel Brunet, 86073 Poitiers Cedex-9, France, Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama 36688, United States
Burkholderia pseudomallei is the bacterium responsible for melioidosis, an infectious disease with high mortality rates. Since melioidosis is a significant public health concern in endemic regions and the organism is currently classified as a potential biothreat agent, the development of effective vaccines and rapid diagnostics is a priority. The capsular polysaccharide (CPS) expressed by B. pseudomallei is a highly conserved virulence factor and a protective antigen. Because of this, CPS is considered an attractive antigen for use in the development of both vaccines and diagnostics. In the present study, we describe the interactions of CPS with the murine monoclonal antibody (mAb) 4C4 using a multidisciplinary approach including organic synthesis, molecular biology techniques, surface plasmon resonance, and nuclear magnetic spectroscopy. Using these methods, we determined the mode of binding between mAb 4C4 and native CPS or ad hoc synthesized capsular polysaccharide fragments. Interestingly, we demonstrated that the O-acetyl moiety of CPS is essential for the interaction of the CPS epitope with mAb 4C4. Collectively, our results provide important insights into the structural features of B. pseudomallei CPS that enable antibody recognition that may help the rational design of CPS-based vaccine candidates. In addition, our findings confirm that the mAb 4C4 is suitable for use in an antibody-based detection assay for diagnosis of B. pseudomallei infections.
synthesis, antigen, capsular polysaccharide, epitope, monoclonal antibodies, MAb, Burkholderia pseudomallei, vaccines, virulence factor, Surface Plasmon Resonance, monoclonal-antibodies
Structure type: homopolymer
Location inside paper: p.2295
Trivial name: 6-deoxy-heptan CPS
Compound class: O-polysaccharide, O-antigen, CPS
Methods: NMR, SDS-PAGE, Western blotting, biological assays, MD simulations, STD NMR, molecular mechanics, SPR, PFG-NMR
Biological activity: the interaction between a specific murine monoclonal antibody, mAb 4C4, and the CPS from B. pseudomallei
3D data: 3D data
NCBI Taxonomy refs (TaxIDs): 28450Reference(s) to other database(s): GTC:G09650IH, GlycomeDB:
3383
Show glycosyltransferases
There is only one chemically distinct structure: