Group B Streptococcus
GBS is a leading cause of neonatal sepsis worldwide. Although prophylactic antibiotics during labor have significantly reduced the incidence for early-onset sepsis (occurring 7> days of life), there are no effective strategies against late-onset sepsis (occurring within 7-90 days of life). A complete picture of late-onset GBS pathogenesis is needed to develop novel prophylactics. We use our robust murine model of late-onset GBS infection, cell culture, and other in vitro techniques to better understand the underlying mechanisms leading to enhanced pathogenesis.
3-D rendering of GBS (magenta) and host cell nuclei (blue) in the small intestine of a GBS-exposed pup 4 days post-infection using confocal microscopy. Credit: Dr. Sophie E. Darch.
GBS, βH/C toxin, & the host intestinal transcriptome.
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.
In this study, our objective was to explore GBS-host interactions in the intestinal environment and determine the contribution of the βH/C toxin. We hypothesized that the βH/C toxin directly modulates gene expression in intestinal epithelial cells and contributes to subsequent translocation of intestinal barriers. Using our robust murine model for late-onset GBS disease, we demonstrate that GBS colonization induces differential gene expression primarily in the colonic epithelium, with toxin-specific effects on genes regulating epithelial cell structure and immune signaling.
Domínguez et al., 2023. Read more here.
GBS & Candida albicans interactions in the intestines.
Candida albicans promotes GBS colonization of host tissues, including the bladder and vagina. However, its impact on GBS colonization of intestinal tissues is unknown. Our laboratory has a well-established mouse model of late-onset GBS disease following postnatal gavage administration of GBS. We adapted this model to study GBS and C. albicans co-colonization in the newborn host. We sought to develop a model of GBS C. albicans co-colonization to study the impact of Candida on GBS intestinal colonization and subsequent systemic dissemination. We found that the presence of C. albicans in the intestinal tract is associated with heavier GBS colonization after exposure. Co-colonization appears to alter the intestinal microenvironment, promoting an expansion of GBS that may predispose to systemic dissemination. Examination of GBS and Candida intestinal co-colonization in human infants may reveal novel risk factors for late-onset GBS disease.
Lindon AK, Domínguez K, Deall T, Randis TM. Candida Promotes GBS Colonization of the Neonatal Gut. Oral Presentation. Pediatric Academic Societies Meeting, April 2023.