# Project 2: Leveraging Metagenomics of the Microbiome to predict colonization/infection by antimicrobial-resistant pathogens

> **NIH NIH P01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $553,418

## Abstract

ABSTRACT
Leveraging Metagenomics of the Microbiome to Predict Colonization/Infection by Antimicrobial-
 Resistant Pathogens (Project #2)
Antimicrobial resistance is a growing, global threat to public health. Vancomycin-resistant enterococci (VRE),
extended spectrum β-lactamase producing/carbapenem-resistant Enterobacteriaceae (ESBL-E/CRE) and
Clostridiodes difficile are key antimicrobial resistant (AMR) pathogens that share the intestine as the initial site
of colonization. Therefore, colonization resistance provided by the commensal microbiota of the intestines is a
critical aspect of the pathophysiology of these organisms. The completion of the initial stages of the Human
Microbiome Project has provided new understanding of how the microbiome impacts infections and has
generated novel tools for further advances in this critical area of human health. Additionally, unbiased
approaches to bacterial identification have resulted in increasing appreciation that VRE, ESBL-E/CRE, and C.
difficile often co-colonize patients suggesting that these organisms are interacting with each other in addition to
the commensal microflora. The long term goals of this project, in synergy with other portions of this P01 proposal,
are to dissect the mechanisms underlying how interactions among the commensal microflora, the host, and VRE,
ESBL-E/CRE, and C. difficile impact intestinal colonization and subsequent infection by these AMR pathogens.
Although it is well known that microbiome disruption by antimicrobials is a key initial step in colonization by these
pathogens, we seek to address the key knowledge gap of why only a subset of patients receiving antimicrobials
become colonized and eventually infected by these organisms. To this end, we propose performing longitudinal
studies of intensive care unit and hematopoietic stem cell transplant patients at two distinct hospitals in the Texas
Medical Center. Patients will be classified depending on both initial and longitudinal colonization status, and
these classifications will be correlated with metagenomics based microbiome analyses of serial stool samples.
In concert with computational biologists, the metagenomics data will be mined for particularly species or
combinations of species that are either protective against or positively associated with colonization and infection,
including co-colonization. Additionally, we will test whether samples from the clinical cohort can protect mice
from AMR pathogen challenge to validate associations observed clinically. Finally, we will also use animal
models to test how pre-existing colonization with a particular organism under study impacts subsequent
colonization by a distinct AMR pathogen. By synergizing with microbiota experts, computational biologists, and
physician-scientists from the highly integrated Gulf Coast Consortium on Antimicrobial Resistance, this proposal
seeks to sharpen understanding of how critical AMR pathogens colonize and infect humans in order to provide
...

## Key facts

- **NIH application ID:** 10024960
- **Project number:** 1P01AI152999-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** SAMUEL A SHELBURNE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $553,418
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10024960

## Citation

> US National Institutes of Health, RePORTER application 10024960, Project 2: Leveraging Metagenomics of the Microbiome to predict colonization/infection by antimicrobial-resistant pathogens (1P01AI152999-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10024960. Licensed CC0.

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