title: Burkholderia pseudomallei Capsular Polysaccharide Recognition by a Monoclonal Antibody Reveals Key Details toward a Biodefense Vaccine and Diagnostics against Melioidosis.
abstract: 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.
authors.affiliation: Department of Chemical Sciences, Università di Napoli Federico II , Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Marchetti
authors.affiliation: Department of Microbiology and Immunology, University of Nevada School of Medicine , Reno, Nevada 89557, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dillon
authors.affiliation: Department of Microbiology and Immunology, University of South Alabama , Mobile, Alabama 36688, United States.
authors.forename: Mary N
authors.initials: MN
authors.lastname: Burtnick
authors.affiliation: Department of Microbiology and Immunology, University of Nevada School of Medicine , Reno, Nevada 89557, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hubbard
authors.affiliation: Université de Poitiers , Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, 4 rue Michel Brunet, 86073 Poitiers Cedex-9, France.
authors.forename: Marielle Tamigney
authors.initials: MT
authors.lastname: Kenfack
authors.affiliation: Université de Poitiers , Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, 4 rue Michel Brunet, 86073 Poitiers Cedex-9, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
authors.affiliation: Université de Poitiers , Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, 4 rue Michel Brunet, 86073 Poitiers Cedex-9, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Gauthier
authors.affiliation: Department of Microbiology and Immunology, University of South Alabama , Mobile, Alabama 36688, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brett
authors.affiliation: Department of Microbiology and Immunology, University of Nevada School of Medicine , Reno, Nevada 89557, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: AuCoin
authors.affiliation: Department of Chemical Sciences, Università di Napoli Federico II , Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lanzetta
authors.affiliation: Department of Chemical Sciences, Università di Napoli Federico II , Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126, Naples, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.affiliation: Department of Chemical Sciences, Università di Napoli Federico II , Complesso Universitario Monte S. Angelo, Via Cintia 4, I-80126, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism*; D016667:Bacterial Capsules / Q000737:chemistry*; D001428:Bacterial Vaccines; D054045:Biological Warfare Agents; D016957:Burkholderia pseudomallei / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008554:Melioidosis / Q000175:diagnosis* / Q000517:prevention & control*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D054045:Biological Warfare Agents