# Role of B cells in controlling Klebsiella pneumoniae associated disease states

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $232,500

## Abstract

SUMMARY
Klebsiella pneumoniae (Kpn) is a primary causative agent of healthcare-associated infections affecting hundreds
of millions worldwide. Bloodstream Kpn infections are of particular concern as they contribute to high patient
mortality and represent a major public health burden. Kpn colonizes the gastrointestinal (GI) tract of healthy and
immunocompromised individuals. In healthy individuals, bacteria can breach the intestinal epithelial surface and
enter the circulatory system, but are rapidly cleared. In patients lacking a fully competent immune system, Kpn
can cause life-threatening systemic infections. There is an urgent need to understand the factors that control the
spread of Kpn from the GI tract to sterile sites. We developed a mouse model of naturally acquired Kpn GI
colonization to identify pathogen and host factors which regulate acquisition, carriage, and dissemination. Using
this mouse model, we found a critical role for B cells in controlling GI bacterial burden, systemic dissemination,
and mortality. In this proposal, we will investigate the mechanisms by which B cells regulate Kpn growth in the
GI tract, translocation, and systemic spread. In Aim 1, we will examine: a) the roles of pre-existing and Kpn-
induced (adaptive) mucosal and systemic antibody in regulating Kpn GI growth and dissemination and b) the
impact of dysbiosis in driving unchecked GI growth and dissemination in B cell-deficient mice. This work will be
complemented by an innovative technical approach in Aim 2 which will reveal bottlenecks and population
dynamics experienced by Kpn along the path from the mouth to the gut to systemic sterile sites in both wild type
and B cell-deficient mice. Here we will leverage a uniquely barcoded Kpn population in combination with high-
resolution sequencing to identify frequencies of translocation events, expansion dynamics, and the origination
of founding populations within distinct tissue sites and blood. Ultimately, this work is expected to reveal the
importance of B cells in controlling Kpn growth and dissemination at various sites within the host and the
mechanisms by which this occurs.

## Key facts

- **NIH application ID:** 10847459
- **Project number:** 5R21AI178595-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Karen M Haas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,500
- **Award type:** 5
- **Project period:** 2023-05-25 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847459

## Citation

> US National Institutes of Health, RePORTER application 10847459, Role of B cells in controlling Klebsiella pneumoniae associated disease states (5R21AI178595-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10847459. Licensed CC0.

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