Vaz Michelle J, Dongas Sophia, Ratner Adam J
Department of Pediatrics, NYU School of Medicine , New York, New York, USA.
Department of Microbiology, NYU School of Medicine , New York, New York, USA.
Microbiol Spectr. 2023 Sep 21;11(5):e0234923. doi: 10.1128/spectrum.02349-23.
Late-onset disease is the most common clinical presentation of Group B (GBS) infection during infancy, and gastrointestinal (GI) colonization is an important precursor. Previously, we described a murine model of postnatal GBS GI colonization that resulted in sustained colonization and progression to invasive disease. Capsular polysaccharide is an important GBS virulence factor. 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 GI colonization. We examined the role of GBS capsule in GI colonization using capsule-producing and acapsular strains derived from GBS strain A909 (serotype Ia) in a murine model. Using isogenic GBS strains differing only in capsular serotypes, we explored the role of specific serotypes in GI colonization by determining competitive indices during cocolonization. We found that GBS A909 colonizes the murine GI tract without causing invasive disease. In monocolonization experiments, there was colonization persistence with the capsule-producing strain (100%) compared to the acapsular mutant strain (13%). In cocolonization experiments, the capsule-producing strain outcompeted its isogenic acapsular mutant, with a geometric mean competitive index of 8, 95% confidence interval (CI) [1.7, 38.9] in the colon at 7 days post-colonization. A909 expressing its native serotype Ia capsule outcompeted an isogenic mutant that expresses serotype III capsule, with a geometric mean competitive index of 2.5, 95% CI [1.2, 5.1] in the colon at 7 days post-colonization. Thus, polysaccharide capsule production enhances GBS GI colonization . In an A909 genetic background, the production of a serotype Ia capsule provides a competitive advantage over an isogenic strain producing type III capsule. The murine model is a valuable tool to understand the role of GBS capsule types in GI colonization. IMPORTANCE The establishment of GBS intestinal colonization is believed to be a critical precursor to late-onset disease in neonates, which has a significant impact on neurodevelopment outcomes in this population. Our prior work described a murine model of postnatal Group B (GBS) acquisition and invasive disease. Using this model, we explored the importance of GBS polysaccharide capsule production on gastrointestinal colonization. We found that the expression of capsule (compared to isogenic acapsular strains) provides an advantage in intestinal colonization and, importantly, that capsule type Ia has an advantage over capsule type III in a GBS A909 strain background. We speculate that specific serotypes may differ in colonization fitness, which may play a role in serotype distribution in neonatal disease.
迟发性疾病是婴儿期B族链球菌（GBS）感染最常见的临床表现，胃肠道（GI）定植是一个重要的先兆。此前，我们描述了一种产后GBS胃肠道定植的小鼠模型，该模型导致持续定植并发展为侵袭性疾病。荚膜多糖是GBS的一种重要毒力因子。基于部分荚膜血清型的疫苗正在进行临床试验。然而，关于特定GBS荚膜血清型在胃肠道定植中的作用知之甚少。我们在小鼠模型中使用源自GBS菌株A909（血清型Ia）的产荚膜菌株和无荚膜菌株，研究了GBS荚膜在胃肠道定植中的作用。使用仅荚膜血清型不同的同基因GBS菌株，我们通过在共定植期间确定竞争指数，探索了特定血清型在胃肠道定植中的作用。我们发现GBS A909定植于小鼠胃肠道而不引起侵袭性疾病。在单一定植实验中，与无荚膜突变菌株（13%）相比，产荚膜菌株的定植持续存在（100%）。在共定植实验中，产荚膜菌株比其同基因无荚膜突变体更具竞争力，在定植后7天，结肠中的几何平均竞争指数为8，95%置信区间（CI）[1.7, 38.9]。表达天然血清型Ia荚膜的A909比表达血清型III荚膜的同基因突变体更具竞争力，在定植后7天，结肠中的几何平均竞争指数为2.5，95%CI [1.2, 5.1]。因此，多糖荚膜的产生增强了GBS在胃肠道的定植。在A909基因背景下，血清型Ia荚膜的产生比产生血清型III荚膜的同基因菌株具有竞争优势。该小鼠模型是了解GBS荚膜类型在胃肠道定植中作用的有价值工具。重要性GBS肠道定植的建立被认为是新生儿迟发性疾病的关键先兆，这对该人群的神经发育结局有重大影响。我们之前的工作描述了一种产后B族链球菌（GBS）感染和侵袭性疾病的小鼠模型。使用该模型，我们探讨了GBS多糖荚膜产生对胃肠道定植的重要性。我们发现荚膜的表达（与同基因无荚膜菌株相比）在肠道定植中具有优势，重要的是，在GBS A909菌株背景下，血清型Ia荚膜比血清型III荚膜具有优势。我们推测特定血清型在定植适应性方面可能存在差异，这可能在新生儿疾病的血清型分布中起作用。
