# Characterizing the Contribution of the Group B Streptococcal Surface Adhesin BspC Interaction with Host Vimentin to Disease and Colonization

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2021 · $33,983

## Abstract

PROJECT SUMMARY
Group B Streptococcus (GBS, also known as Streptococcus agalactiae) is a Gram-positive, -hemolytic
bacterium normally found in the human gastrointestinal and urogenital tracts. GBS remains a leading cause of
invasive disease in newborns and certain adult populations including pregnant women. The development of
GBS disease is initiated by the asymptomatic colonization of the female genital tract and during pregnancy can
be associated with chorioamnionitis, puerperal endometritis and preterm labor. Approximately 20-30% of
healthy women are colonized rectovaginally with GBS; the majority of infants born to these women will
themselves become colonized with the bacterium. Newborn infection also results from ascending infection of
the bacterium through the placental membranes to initiate infection in utero. GBS is the principle etiologic
agent of neonatal bacterial meningitis, and GBS meningeal infection results in 10-15% mortality despite
antibiotic treatment. Additionally, up to 40% of survivors develop permanent neurological sequelae, including
cognitive defects, seizure activity, and cerebral ischemia. To access the central nervous system (CNS) and
cause meningitis blood-borne GBS must penetrate the blood-brain barrier (BBB); however, little is known about
the very first and crucial interaction between GBS and the BBB that initiates bacterial crossing and disease
progression. This proposal seeks to characterize the role of a newly identified GBS Antigen I/II family adhesin,
BspC, to the pathogenesis of colonization and CNS disease. We have recently determined that BspC
promotes attachment to BBB endothelium and contributes to the development of GBS meningitis. Further we
have discovered that BspC interacts directly with vimentin, a widely distributed intermediate filament protein
found in blood vessel endothelial cells. Thisproposal seeks toidentify the region on BspC that interacts with
vimentin, and to characterize the role of this interaction in GBS meningitis and colonization of the female
reproductive tract. I hypothesize that the binding region is contained within the globular variable domain (V-
domain) of BspC and contributes to both GBS meningitis and vaginal colonization/ascending infection. These
hypotheses will be addressed with both in vitro and in vivo models of BBB penetration and vaginal colonization
in the following specific aims: Aim 1: Identify the critical regions and amino acids required for BspC V-domain-
vimentin interaction; Aim 2: Characterize the role of BspC and vimentin in the female reproductive tract. These
data will clarify the crucial role of Antigen I/II proteins to GBS colonization and disease and provide
fundamental mechanistic insights that may inform new treatment strategies to prevent colonization and
ultimately bacterial meningitis.

## Key facts

- **NIH application ID:** 10312484
- **Project number:** 1F31AI164674-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Haider Syed Manzer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,983
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312484

## Citation

> US National Institutes of Health, RePORTER application 10312484, Characterizing the Contribution of the Group B Streptococcal Surface Adhesin BspC Interaction with Host Vimentin to Disease and Colonization (1F31AI164674-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312484. Licensed CC0.

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