# Elucidating transmission of plasmids harboring blaKPC among carbapenem-resistant Enterobacteriaceae using long-range sequencing

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $194,724

## Abstract

PROJECT SUMMARY/ABSTRACT:
Rationale: Resistance to broad-spectrum carbapenem antibiotics has spread rapidly among
Enterobacteriaceae since the early 1990s, posing an escalating threat to medical care. While Klebsiella
pneumoniae comprise the majority of CRE in the United States, recent evidence suggests that CRE are rapidly
diversifying. This reflects the ability of carbapenem resistance genes to spread to between different strains of
Enterobacteriaceae via mobile genetic elements, particularly plasmids. Despite their important infection control
implications, the mechanisms by which these plasmids spread have not been fully elucidated. Candidate: As
an infectious diseases clinician with a masters’ degree in biostatistics, Dr. Angela Gomez-Simmonds’ previous
publications characterize the clinical and molecular epidemiology of CRE. Formal training in advanced
bioinformatics and genomic epidemiology will be critical for the completion of the proposed research and the
advancement of her career. With primary mentor Dr. Anne-Catrin Uhlemann, she has assembled a
multidisciplinary advisory team of experts to guide her training and research progress. Dr. Gomez-Simmonds’
long-term goal is to become an NIH-funded independent researcher using next-generation sequencing to
understand links between the bacterial evolution, resistance mechanisms, and clinical epidemiology of
multidrug-resistant Gram-negative nosocomial pathogens. Environment: The Uhlemann laboratory at
Columbia University Medical Center (CUMC) has the microbiology and sequencing tools necessary to carry
out the proposed research, as well as a large retrospective collection of CRE clinical isolates from diverse sites
to perform genomic studies. CUMC has a strong track record of supporting the career development of young
physician-scientists. Approach: We hypothesize that horizontal transfer of plasmids encoding blaKPC, the
dominant carbapenem resistance gene in the United States, is an important contributor to the spread of CRE
within hospitals. To overcome limitations in previous genomics studies using traditional sequencing platforms
such as Illumina, we will perform long-range plasmid sequencing. Plasmid-mediated transmission of blaKPC will
be characterized through three aims. In Aim 1 we will systematically assess the contribution of horizontal
transfer to the spread of CRE in a large retrospective collection of CRE isolates collected between 2009-2016.
In Aim 2 we will perform a case-control-control study to assess unique clinical risk factors associated with
horizontal transfer versus clonal spread; a third control group will consist of CRE-negative patients. In Aim 3
we will determine whether hospital environmental surfaces such as sink drains are reservoirs for blaKPC-
harboring plasmids. Phylogenetic analyses will be used to assess links between plasmid sequences from
clinical and environmental CRE and published genomes. In addition to elucidating the role of plasmids in the
diversifica...

## Key facts

- **NIH application ID:** 10057217
- **Project number:** 5K23AI137316-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Angela Gomez-Simmonds
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,724
- **Award type:** 5
- **Project period:** 2018-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057217

## Citation

> US National Institutes of Health, RePORTER application 10057217, Elucidating transmission of plasmids harboring blaKPC among carbapenem-resistant Enterobacteriaceae using long-range sequencing (5K23AI137316-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057217. Licensed CC0.

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