# Dynamics of Pseudomonas aeruginosa During Bacteremia

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $237,000

## Abstract

Pseudomonas aeruginosa (PA) is the third most common gram-negative etiology of bloodstream infections,
and these infections are associated with a crude mortality rate of 39%. Despite their frequency and severity,
PA bloodstream infections are relatively poorly understood compared to pneumonia, burn infections, and
keratitis. To investigate the pathogenesis of PA bloodstream infections, we have used a mouse model in which
the tail vein is injected with a library of barcoded bacteria. Our preliminary experiments yielded several
unexpected findings. First, in approximately half of severely ill bacteremic mice, the PA bacteria found
disseminated throughout the body were descendants of just a few bacterial cells, suggesting that only a small
number of the PA in the initial inoculum persisted and disseminated to cause severe disease. Second, PA
bacteria in the blood migrated through a tight bottleneck to the gallbladder, which was a protective niche that
allowed for a small number of PA to replicate to extremely high numbers. From there, these descendants of
just a few PA bacteria seeded the intestines, presumably by passing through the common bile duct. This
finding is particularly interesting in the context of other reports suggesting that PA is capable of migrating from
the intestines to the bloodstream. Together, these observations suggest the intriguing hypothesis that spread
of PA from the bloodstream to the intestines and back to the bloodstream may generate a "positive feedback
loop" in which the gallbladder serves as an amplifier of PA numbers. In this application, we propose to address
this limitation and directly test our hypothesis by performing the following specific aims: (1) Characterize
bacterial dynamics over the course of PA bloodstream infections. (2) Determine whether interventions
that disrupt PA transit through the intestines improve outcomes in bloodstream infections. Completion
of these aims has the potential to uncover novel pathogenic mechanisms that contribute to the poor outcomes
observed in PA bloodstream infections. The impact of these studies is three-fold: (i) they may provide a
rationale for examining the pathogenesis of bloodstream infections caused by bacteria other than PA; (ii) the
knowledge gained may be used as a foundation and justification for costlier and more laborious studies in
humans with PA bloodstream infections; and (iii) these studies may inform novel therapeutic interventions that
lower the unacceptably high mortality rates currently associated with PA bacteremia.

## Key facts

- **NIH application ID:** 10042352
- **Project number:** 1R21AI153953-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ALAN R HAUSER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2020-07-24 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042352

## Citation

> US National Institutes of Health, RePORTER application 10042352, Dynamics of Pseudomonas aeruginosa During Bacteremia (1R21AI153953-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10042352. Licensed CC0.

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