Structural Characterization of S. Neumoniae’s Capsular polysacharide 14 using a combination of NMR and Multiscale simulations
Humberto C. Gonzalez and Sergio Pantano
Institut Pasteur de Montevideo, UruguayCarbohydrates and Glicoconjugates Laboratory - Hygiene Institute, Montevideo, Uruguay.
S.pnemoniae is the leading cause of extra-hospital pneumonia and a wide range of pathologies such as sinusitis, meningitis, osteoarticular infections and endocarditis. These bacteria are encapsulated by repetitive branched polysaccharides, which are crucial for pathogenicity and infectivity, constituting a physical barrier between the host’s immune system and the bacteria itself. Among several serotypes, 14 (CPS14) has been identified as the most prevalent in South America. Aimed to acquire structural information on CPS14 we carried out a combination of experimental and multiscale simulation studies. Characterization of the native polysaccharide was done through HPLC-MALLS and NOE-NMR experiments. Then a set of combined Coarse-grained/atomistic molecular dynamics simulations with different polymer lengths and concentrations were performed, reaching dimensions comparable with those of the native polysaccharide size. Multiscale simulations brought forth a vast conformational diversity helping to rationalize the structural data from NOE-NMR assays, suggesting that the native CPS14 exists in a globular, and plastic conformation lacking repetitive or long-range structured conformational motifs.
