Neonatal Infectious Diseases/Immunology
Neonatal Infectious Diseases/Immunology 3
Kristen Dominguez (she/her/hers)
University of South Florida
Tampa, Florida, United States
Group B Streptococcus (GBS) is a leading cause of infant sepsis worldwide. Colonization of the gastrointestinal tract is a critical precursor to late-onset disease in exposed newborns. Neonatal susceptibility to GBS intestinal translocation stems from intestinal immaturity; however, the mechanisms by which GBS exploits the immature host remain unclear. β-hemolysin/cytolysin (βH/C) is a highly conserved, pore-forming toxin produced by GBS capable of disrupting extraintestinal epithelial barriers, with unknown roles in intestinal barrier disruption. Our previous experiments suggest that βH/C does not contribute to intestinal colonization but does impact GBS dissemination (unpublished).
Objective: Here, our aim was to identify the impact of GBS and βH/C on the host intestinal transcriptome.
We used an established mouse model of postnatal GBS acquisition. Animals were gavaged with GBS COH-1 serotype III ST-17 (WT), its isogenic βH/C-deficient mutant COH1delcylE (KO), or PBS as a vehicle control. Intestines were harvested at 4 days post-exposure and processed for intestinal epithelial cell isolation and RNA isolation. We used RNA-seq to compare expression profiles of intestinal epithelial cells and analyzed functional changes using KEGG pathway analysis.
We found that GBS colonization leads to major transcriptomic changes in the colon, but not the small intestine (Figure 1A). There were significant differences in gene expression among the 3 groups. Those in the KO group indicate toxin-specific changes in host gene expression (Figure 1B). Using KEGG analysis, we identified 46 KEGG pathways that were significantly altered between the WT and PBS groups in the colon (false discovery rate < 0.05). Among those pathways, 7 were involved in epithelial barrier structure and function (Figure 2A) and 14 involved in immune regulation (Figure 2B).
Overall, our results reveal a significant effect of GBS colonization on the colonic transcriptome with major functional changes being attributed to barrier and immune function. Toxin-induced changes in genes may underlie mechanisms that lead to enhanced GBS translocation and subsequent late-onset disease.