# Project 2 Defining multiscale dynamics of strains, genes and resistance in bacterial pathogens

> **NIH NIH U19** · BROAD INSTITUTE, INC. · 2021 · $750,173

## Abstract

Project Summary
Bacterial diseases kill millions of people worldwide each year, despite the advent of antibiotics
90 years ago. Emergence and spread of new and rapidly evolving pathogens with increased
virulence, resistance to antibiotics, and transmissibility is increasingly straining efforts to
manage infections and save lives. To combat this trend, we need a comprehensive and
systematic understanding of the complex dynamics between the host, including host microbiota,
and pathogen at every level of interaction—cellular, individual, and population levels. Our
proposed studies leverage recent advances in sequencing technologies, innovative
high-throughput molecular and multi-omic approaches, access to unique patient cohorts, and
novel computational methods to characterize the genomes, transcriptomes, and individual
strain-level interactions of bacterial pathogens with their hosts and other microbiota. In
collaboration with renowned infectious disease researchers, clinicians, and epidemiologists, we
will target critical gaps in our understanding of key infectious disease threats—uropathogenic
E​scherichia coli (UPEC), carbapenem resistant ​Enter​obacteriaceae (CRE), and multidrug
resistant enterococci. Specifically, we will i)​ ​determine the gut-to-urinary tract dynamics of UPEC
in recurrent urinary tract infections; ii) track the multiscale dynamics of antibiotic resistance
gene proliferation - from individual microbiota to local and global circulation; and iii) characterize
the dynamic functional reservoir of MDR enterococci. While our aims focus on ESKAPE
pathogens, our goal is to pioneer and disseminate a ​comprehensive​ ​technological framework
and resources to empower clinical and research communities working to understand, diagnose,
prevent, and treat infectious diseases.

## Key facts

- **NIH application ID:** 10163678
- **Project number:** 5U19AI110818-08
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Ashlee Miriam Earl
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $750,173
- **Award type:** 5
- **Project period:** 2014-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163678

## Citation

> US National Institutes of Health, RePORTER application 10163678, Project 2 Defining multiscale dynamics of strains, genes and resistance in bacterial pathogens (5U19AI110818-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163678. Licensed CC0.

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