Bridging the gap: organotypic models to study late-onset group B streptococcus infection
Summary
Group B Streptococcus (GBS) is a major cause of neonatal sepsis worldwide. Gastrointestinal colonization by GBS is an important risk factor for late-onset disease in newborns. Most studies of GBS pathogenesis rely on animal models with limited human relevance or use immortalized adult human cells that do not recapitulate the unique genetic and phenotypic features of the neonatal intestinal epithelium. Previous studies using tissue-derived human intestinal enteroids (HIEs) and induced pluripotent stem cell-derived human intestinal organoids (HIOs) to model host interactions with enteric pathogens have yielded valuable insights. Here, we describe the use of GBS-exposed HIEs and HIOs to study GBS interactions with the immature human intestinal epithelium. Using these models, we demonstrated that GBS induces changes in gene expression of both HIEs and HIOs that are distinct from what has been reported in immortalized adult cell lines. We observed GBS attachment to the apical surfaces of HIEs and HIOs and, in some cases, translocation across intestinal epithelial barriers. To examine the impact of GBS exposure on intestinal barrier function, we generated polarized HIE monolayers on Transwell plates. We observed GBS translocation across monolayers, accompanied by a trend in increased epithelial barrier permeability reflected by decreased transepithelial electrical resistance. These data demonstrate that both HIEs and HIOs are robust and useful models for studying the pathogenesis of late-onset GBS infection in the vulnerable newborn host. Importantly, they provide a much-needed platform to test novel preventative strategies.IMPORTANCEGroup B Streptococcus (GBS) is a major cause of infectious morbidity and mortality in neonates. Late-onset GBS disease, which develops after the first week of life, arises when GBS colonizes the neonatal gut and compromises intestinal barriers, resulting in systemic infection. Studies investigating the pathogenesis of late-onset GBS disease typically employ animal models or in vitro immortalized adult human intestinal cell lines, which can limit the applicability of findings to human neonates. In this study, we introduce the use of three-dimensional fetal tissue-derived human intestinal enteroids and induced pluripotent stem cell-derived human intestinal organoids to study GBS-host interactions within the gut. These novel models demonstrate improved ability to recapitulate the vulnerability of the immature human host and function as a platform to test novel interventional strategies to protect exposed newborns.
| Authors | Pearah AN, John-Lewis Edwards N, Carter RR, Worthington L-AM, Huszar MR, Domínguez K, Wapshott-Stehli HL, Lindon AK, Darch SE, Ho TTB, Randis TM |
|---|---|
| Journal | Microbiology spectrum |
| Publication Date | 2026 Jun 2;14(6):e0231625 |
| PubMed | 42017661 |
| PubMed Central | PMC13228084 |
| DOI | 10.1128/spectrum.02316-25 |