# Characterization of a Type VII Secretion System in Group B Streptococcus and its Role in Virulence and Immune Response

> **NIH NIH K22** · UNIVERSITY OF VIRGINIA · 2024 · $162,000

## Abstract

PROJECT SUMMARY
Group B Streptococcus (GBS) remains the leading etiologic agent of neonatal bacterial meningitis and a major
opportunistic pathogen in certain adult populations, including pregnant women. During pregnancy, GBS
asymptomatically colonizes the vaginal tract of 20-30% of healthy women but can be transmitted to the neonate
in utero or during birth resulting in neonatal meningitis upon GBS disruption of the blood-brain barrier (BBB) and
10-15% mortality, regardless of antibiotic treatment. Despite this major public health concern, the
mechanisms
 specific
by which Group B streptococcal effectors mediate toxicity and drive inflammatory responses during
colonization and development of meningitis are still being elucidated. Type VII secretion systems (T7SS) have
been identified in Actinobacteria and Firmicutes and shown to secrete
functions
GBS
lacking
highly immunogenic effector proteins with
in virulence, host toxicity, or interbacterial killing; however, a T7SS had never been characterized in
 and our analysis suggests that GBS encodes unique T7SS effectors. My recent work shows that GBS
the ATPase EssC (which drives T7SS) or the secreted T7 effector EsxA areattenuated in murine models
of meningitis and reproductive tract ascending infection and exhibit decreased cytotoxicity in brain endothelium.
We have further shown that EsxA is a pore-forming protein, possibly mediating T7SS-dependent cytotoxicity.
Finally, my recent work suggests that IL-17 is important for clearance of GBS during vaginal colonization and
may be dampened by the T7SS resulting in GBS immune evasion. Based on these data, this K22 proposal seeks
to identify GBS T7-secreted effectors and elucidate the mechanism by which they mediate promote host toxicity
and elicit immune responses during GBS disease progression and colonization. These questions will be
addressed with both in vitro and in vivo models of GBS vaginal colonization and BBB penetration in the following
specific aims:
AIM 1: Elucidate the mechanism of GBS EsxA pore-formation and host cytotoxicity.
AIM 2: Identify and characterize the GBS T7SS secretome.
AIM 3: Evaluate the T7SS-dependent IL-17 responses to GBS in the female reproductive tract
This proposal is the first to characterize GBS T7SS effectors and their role in both GBS colonization and
pathogenesis and may afford novel targets and alternative therapeutic strategies to treat and prevent GBS
disease.

## Key facts

- **NIH application ID:** 10739232
- **Project number:** 1K22AI170795-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Brady L Spencer
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $162,000
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739232

## Citation

> US National Institutes of Health, RePORTER application 10739232, Characterization of a Type VII Secretion System in Group B Streptococcus and its Role in Virulence and Immune Response (1K22AI170795-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10739232. Licensed CC0.

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