Bridging the gap: organotypic models to study late-onset group B streptococcus infection

Area of Science:

• Microbiology and Immunology
• Gastroenterology and Hepatology
• Developmental Biology

Background:

• Group B Streptococcus (GBS) is a leading cause of neonatal sepsis worldwide.
• Gastrointestinal colonization by GBS is a significant risk factor for late-onset disease in newborns.
• Existing models using animal or adult human cell lines lack relevance for studying neonatal GBS pathogenesis.

Purpose of the Study:

• To investigate GBS interactions with the immature human intestinal epithelium using novel organoid models.
• To assess the impact of GBS on intestinal barrier function in a human neonatal context.
• To establish a relevant platform for testing preventative strategies against GBS infection.

Main Methods:

• Utilized human intestinal enteroids (HIEs) and human intestinal organoids (HIOs) derived from fetal tissue and induced pluripotent stem cells, respectively.
• Exposed HIEs and HIOs to GBS to analyze gene expression changes and pathogen-host interactions.
• Generated polarized HIE monolayers on Transwell plates to evaluate GBS translocation and effects on epithelial barrier integrity (measured by transepithelial electrical resistance).

Main Results:

• GBS exposure induced distinct gene expression changes in HIEs and HIOs compared to adult cell lines.
• Observed GBS attachment to the apical surface and translocation across HIEs and HIOs.
• GBS translocation across HIE monolayers correlated with increased epithelial permeability and decreased transepithelial electrical resistance.

Conclusions:

• HIEs and HIOs serve as robust and relevant models for studying GBS pathogenesis in the neonatal gut.
• These models accurately recapitulate the vulnerability of the immature intestinal epithelium to GBS.
• The developed models provide a valuable platform for evaluating novel interventions against late-onset GBS disease.