# P2-The impact of genetic background on the emergence and spread of carbapenem-resistant Enterobacterales

> **NIH NIH U19** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $1,434,278

## Abstract

Project Summary – Project 2 (Bacteria)
Carbapenem-resistant Enterobacterales (CRE) has been designated as an urgent antibiotic resistance threat
by both the U.S. Centers for Disease Control and Prevention and the World Health Organization. The basis for
this notoriety is the propensity for CRE to cause outbreaks among vulnerable hospitalized patients, high
mortality rates for infected patients, and the emergence of strains of CRE that are resistant to virtually all
available antibiotics. The most problematic strains of CRE are those that have become carbapenem-resistant
via the acquisition of a carbapenemase gene that can cleave most beta-lactam antibiotics. These
carbapenemase genes are most often carried on plasmids, and through conjugation have disseminated widely
among diverse members of the Enterobacterales order. Given the great diversity of CRE observed in
healthcare settings, a critical need from a public health surveillance perspective is the ability to assess the risk
posed by a newly detected strain. We reason that the risk of a newly emerged CRE strain is dictated by: i) the
stability of its association with the carbapenemase containing plasmid, ii) it’s capacity to disseminate this
plasmid to other Enterobacterales, iii) the potential of the CRE strain to evolve resistance to additional front-line
antibiotics, and iv) its potential to colonize, infect and spread among vulnerable patient populations. We
present preliminary data that all four of these components of risk can vary among even closely related strains
of CRE isolated from patients. Motivated by this, in this project we will first experimentally quantify the variation
in these four determinants of risk in longitudinal collections of CRE collected from two healthcare networks in
the U.S. and employ bacterial genome-wide association studies (bGWAS) to identify genetic variation
associated with each of these four phenotypes. Next, we will take advantage of the longitudinal nature our
sample collections, and the availability of relevant patient meta-data, to quantify the degree to which variation
in risk potential predicts patterns of CRE strain emergence, resistance evolution and spread. We expect this
project to contribute substantially to our understanding of how genetic variation in CRE influences its epidemic
potential. Looking forward, the ability to experimentally quantify the components of risk, and ultimately identify
genetic signatures of these phenotypes, would greatly enhance the capacity of public health genomic
laboratories to make proactive, instead of reactive risk assessments, and thereby contain emerging threats.

## Key facts

- **NIH application ID:** 10852058
- **Project number:** 1U19AI181767-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Evan Snitkin
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,434,278
- **Award type:** 1
- **Project period:** 2024-06-14 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852058

## Citation

> US National Institutes of Health, RePORTER application 10852058, P2-The impact of genetic background on the emergence and spread of carbapenem-resistant Enterobacterales (1U19AI181767-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852058. Licensed CC0.

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