Randis, T. M. | bioRxiv Science

bioRxiv2026

Microbial Crosstalk in the Neonatal Gut: Candida albicans Impacts Group B Streptococcus Pathogenicity

Background Group B Streptococcus (GBS) is a leading cause of bacterial sepsis globally. Late-onset (LO) GBS disease is preceded by colonization within the gastrointestinal tract in vulnerable neonates. Previous studies demonstrate that Candida albicans (C. albicans) promotes GBS colonization of host tissues including the bladder and vagina. However, its impact on GBS colonization of the intestinal tract is unknown. Methods We established a new animal model to study GBS and C. albicans co-colonization model in the context of the newborn host to examine C. albicans impact on GBS and further evaluated fluconazole prophylactic treatment to these same outcomes. Physical interactions between organisms in vivo were imaged and GBS gene expression was evaluated. Results C. albicans increased GBS burden in the neonatal gut and GBS was physically colocalized with C. albicans hyphae as evidenced by the colocalization analysis. Fluconazole treatment of co-colonized mice decreased extraintestinal GBS dissemination. C. albicans presence upregulated genes encoding proteins responsible for GBS adhesion and invasion of intestinal epithelial cells. Conclusion C. albicans enhances GBS burden and pathogenicity in the neonatal gut. These findings highlight the need for further investigation into C. albicans as a potential risk factor for GBS colonization and LO disease in human infants.

microbiology↗

bioRxiv2023

Group B Streptococcus drives major transcriptomic changes in the colonic epithelium.

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. {beta}-hemolysin/cytolysin ({beta}H/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 {beta}H/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 {beta}H/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. RNA-sequencing was used to examine the transcriptomes of host cells followed by gene ontology enrichment and KEGG pathway analysis. A separate cohort of animals was followed longitudinally to compare colonization kinetics and mortality between WT and KO groups. We demonstrate that dissemination to extraintestinal tissues occurred only in the WT exposed animals. We observed major transcriptomic changes in the colons of colonized animals, but not in the small intestines. We noted differential expression of genes that indicated the role of {beta}H/C in altering epithelial barrier structure and immune response signaling. Overall, our results demonstrate an important role of {beta}H/C in the pathogenesis of late-onset GBS disease.

microbiology↗