# Project 3: Functional Microbiome and Host Signatures in Transition from Commensal to pathogen

> **NIH NIH P01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $539,460

## Abstract

ABSTRACT
 Project 3: Functional Microbiome and Host Signatures in Transition from Commensal to pathogen
Overuse of antibiotics and adaptability of bacteria has resulted in antimicrobial resistance (AMR) in pathogens
of significant public health concern. Identifying individuals who are susceptible to infection is critical in
implementing an effective treatment plan and in promoting good antimicrobial stewardship. This project focuses
on developing innovative systems technology to develop microbiome-based risk algorithms that identify
susceptible patients in the general hospitalized population. The project premise being tested is that nosocomial
pathogens that colonize the intestines specifically target individuals with immature infant-like gut microbiota
features that are permissive to pathogen colonization. The notable AMR-pathogens of our study include
Clostridioides difficile, vancomycin-resistant enterococcus (VRE), carbapenem-resistant Klebsiella pneumoniae,
and extended spectrum β-lactamase producing Enterobacteriacae (ESBL-E/CRE) because these organisms
often colonize the intestines before causing infection. Specifically, we show that these priority pathogens often
co-colonize vulnerable patients who are missing keystone microbiota species that appear to be broadly
protective against these bacteria by producing diverse bacteriocins. In Project 3 of this PO1 application, we will
perform synergistic functional profiling of these unique host-microbiota-pathogen interactions to address the
following two specific aims:
 • Aim 3.1. Define the metabolically active microbiota community structure identified with
 pathogen colonization and disease progression in the susceptible patient.
 • Aim 3.2. Characterize keystone microbiota features and their protective antimicrobial
mechanisms.
The study is impactful because we intend to establish predictive microbiome-risk algorithms for precision
infection management of immunosuppressed and critically ill patients. The long-term goal is to advise the
physician and healthcare stakeholders of clinical surveillance and therapeutic interventions that match the risk
posed by each individual’s infection, as well as define host-microbiota-pathogen interactions that are permissive
to other emerging infections.

## Key facts

- **NIH application ID:** 10226289
- **Project number:** 5P01AI152999-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Tor C. Savidge
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $539,460
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226289

## Citation

> US National Institutes of Health, RePORTER application 10226289, Project 3: Functional Microbiome and Host Signatures in Transition from Commensal to pathogen (5P01AI152999-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226289. Licensed CC0.

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