402 - Elucidating the role of Group B Streptococcus Capsular Serotypes in a murine model of intestinal colonization

Poster Number: 402
Publication Number: 402.334

Michelle J. Vaz, Hassenfeld Children's Hospital at NYU Langone, Tenafly, NJ, United States; Sophia A. Dongas, NYU Lagone Health, Astoria, NY, United States; Adam J. Ratner, NYU Grossman School of Medicine, New York, NY, United States

Background: Late-onset disease (LOD) is the most common clinical presentation of Group B Streptococcus (GBS) infection during infancy, where gastrointestinal (GI) colonization is an important precursor. Our prior work described a postnatal murine model of GBS GI colonization that resulted in sustained colonization and progression to invasive disease. Using this model, we can elucidate the role of specific bacterial and host factors that influence disease phenotype. Capsular polysaccharide is an important GBS virulence factor, and vaccines based on a subset of capsular serotypes are in clinical trials. However, little is known regarding the role of specific GBS capsular serotypes in the setting of GI colonization and LOD.

Objective: To determine the role of GBS capsular polysaccharide and specific serotypes in murine GI colonization.

Design/Methods: We used previously generated isogeneic GBS strains, differing only in capsule serotype in an A909 (ST7, serotype Ia) genetic background in a murine model of GI colonization. Briefly, animals (12-14 days of life) were orally infected with GBS strains; euthanasia was performed and the GI tract was harvested at 3,7 and 14 days post infection in all experimental cohorts. We examined the role of capsule on GBS burden in the GI tract using capsule-producing and acapsular strains. We explored the role of different serotypes, independent of other factors, in GI colonization by determining competitive indices during co-colonization experiments.

Results: GBS A909 colonizes the murine GI tract. The capsule-producing strain efficiently outcompetes its isogenic acapsular mutant (geometric mean exceeding 7, 95% CI [1.7, 38.9] at 7 days post colonization) (Figure A). A909 expressing native serotype Ia capsule outcompetes its isogenic mutant that expresses serotype III capsule (geometric mean of 4, 95% CI [1.2, 5.1] at 7 days post colonization) (Figure B).

Conclusion(s):

Polysaccharide capsule production enhances GBS GI colonization in vivo. In an A909 genetic background, production of serotype Ia capsule provides a competitive advantage over an isogenic strain producing a type III capsule. The murine model is a valuable tool to understand the role of GBS capsule types in GI colonization and progression to invasive disease.