# Hepatic survival and population dynamics of extraintestinal pathogenic Escherichia coli

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2021 · $39,551

## Abstract

ABSTRACT
Extraintestinal Pathogenic Escherichia coli (ExPEC) comprise a broad group of E. coli isolates that cause
disease outside of the intestine and are among the most common causes of clinical bacteremia in humans. Most
bacteria that gain access to the circulatory system are captured and killed by tissue-resident macrophages in
the liver. In contrast to related commensal and intestine-restricted pathogenic E. coli, ExPEC isolates possess
mechanisms to survive longer within these hepatic defenses. To uncover genes underlying such mechanisms,
we performed a genome-scale transposon insertion sequencing screen on ExPEC isolated from murine livers
following intravenous injection of mice with an ExPEC transposon insertion library. This screen uncovered a core
set of genes required for optimal ExPEC fitness in the liver, ~90% of which encode components or regulators of
the cell envelope. Unexpectedly, analysis of the population-level distribution of transposon-insertion mutants
revealed that a random subset of the bacteria within the liver expands clonally. Together, these observations
underlie the two central hypotheses that will be explored in this proposal: 1) ExPEC pathways that control distinct
cell envelope homeostasis axes protect bacteria against liver macrophages to maintain bacterial survival, and
2) interactions between liver macrophages and specific bacterial genes that support intra-hepatic survival govern
how the pathogen is distributed within the host during clearance. Findings from the proposed studies, which rely
on both pathogen- and host-centric approaches, will provide knowledge of how ExPEC survive within and are
cleared from extraintestinal organs. Ultimately, these fundamental insights may assist in the development of
therapeutic strategies to accelerate clearance of systemic infections.

## Key facts

- **NIH application ID:** 10129628
- **Project number:** 1F31AI156949-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Karthik Hullahalli
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,551
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129628

## Citation

> US National Institutes of Health, RePORTER application 10129628, Hepatic survival and population dynamics of extraintestinal pathogenic Escherichia coli (1F31AI156949-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129628. Licensed CC0.

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