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| Status |
Public on May 31, 2023 |
| Title |
Group B Streptococcus drives major transcriptomic changes in the colonic epithelium |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 toxin produced by GBS capable of disrupting epithelial barriers. However, its role in the pathogenesis of late-onset GBS disease is unknown. Our aim was to determine the contribution of βH/C to intestinal colonization and translocation to extraintestinal tissues. Using our established mouse model of late-onset GBS disease, we exposed animals to GBS COH-1 (WT), a βH/C-deficient mutant (KO), or vehicle control (PBS) via gavage. Blood, spleen, brain, and intestines were harvested 4 days post-exposure for determination of bacterial burden and isolation of intestinal epithelial cells. We used RNA-sequencing to examine the transcriptomes and performed gene ontology enrichment and KEGG pathway analysis. A separate cohort of animals were followed longitudinally to compare colonization kinetics and mortality between WT and KO groups. We demonstrate that disseminated to extraintestinal tissues occurred only in the WT exposed animals. We observed major transcriptomic changes in the colon of colonized animals, but not in the small intestine. We noted differential expression of genes among WT and KO exposed mice indicating that βH/C contributes to alterations in epithelial barrier structure and immune response signaling. Overall, our results demonstrate an important role for βH/C in the pathogenesis of late-onset GBS disease.
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| Overall design |
RNA-Seq
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| Contributor(s) |
Domínguez K, Lindon AK, Gibbons JA, Darch SE, Randis TM |
| Citation(s) |
37278645 |
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| Submission date |
Apr 28, 2023 |
| Last update date |
Aug 30, 2023 |
| Contact name |
Kristen Dominguez |
| E-mail(s) |
kdominguez@usf.edu
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| Phone |
3057960973
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| Organization name |
University of South Florida
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| Department |
Molecular Medicine
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| Lab |
Randis Lab
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| Street address |
9440 leatherwood ave
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| City |
tampa |
| State/province |
FL |
| ZIP/Postal code |
33647 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (25)
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| Relations |
| BioProject |
PRJNA962863 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230856_deseq2_norm_counts.xlsx |
8.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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