# How Do a Few Attached Staphylococcus aureus Bacteria Evade Innate Immunity to Initiate Biofilm Infection on an Implanted Medical Device?

> **NIH NIH R56** · MONTANA STATE UNIVERSITY - BOZEMAN · 2021 · $510,586

## Abstract

PROJECT SUMMARY/ABSTRACT
Implanted medical devices have saved lives and improved the quality of life for many. But such
implants remain vulnerable to troublesome infection by microorganisms that aggregate on or near the
device in a biofilm. More than three decades of work on antimicrobial coatings and antibiotic therapies
have failed to produce robust solutions to biofilm infection, suggesting that researchers have been
missing an essential piece of this puzzle. We contend that the key to preventing implant-related
infection is a better understanding and orchestration of innate immunity at the earliest stage. In
particular, it is hypothesized that slow recruitment of neutrophils to a sparsely contaminated biomaterial
gives some bacteria time to grow into aggregates, and that these aggregates are protected from killing
by neutrophils and persist. In three Specific Aims, this project will quantify the following phenomena:
Aim 1. Neutrophil recruitment times to bacteria-contaminated biomaterial surfaces. Aim 2. Growth
dynamics of bacteria attached to an abiotic surface prior to neutrophil discovery. Aim 3. Bacterial and
neutrophil fates post neutrophil discovery. These measurements will be made by an interdisciplinary
team merging expertise in quantitative biochemical engineering, molecular microbiology, immunology,
orthopedic surgery, biomaterials, and mathematics and statistics. The primary model bacterium will be
Staphylococcus aureus and the animal models will all be in mice. Four complementary experimental
models will be used: 1) in vitro video microscopy of bacteria-human neutrophil interactions on a
sparsely inoculated abiotic surface; 2) whole animal imaging of neutrophil and bacterial dynamics
following subcutaneous implantation; 3) intravital imaging with single cell resolution of neutrophil-
bacteria dynamics on a subcutaneous implant, and 4) a conventional subcutaneous implant model to
be used for cytokine/gene profiling, cataloging of immune cell types present, and additional microscopy.
This project will generate unique data sets emphasizing quantitative, probabilistic characterization of
the host-pathogen interaction in the first several hours after implantation, the likely window for
preventing a biofilm infection from establishing. This work will open the door to new strategies for
preventing infections on implanted medical devices by boosting neutrophil numbers or speeding up
their delivery to the contaminated implant with multiple potential advantages: short-term intervention,
broad spectrum applicability, and obviation of antibiotic resistance concerns.

## Key facts

- **NIH application ID:** 10387835
- **Project number:** 1R56AI155692-01
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** PHILIP S STEWART
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $510,586
- **Award type:** 1
- **Project period:** 2021-06-07 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387835

## Citation

> US National Institutes of Health, RePORTER application 10387835, How Do a Few Attached Staphylococcus aureus Bacteria Evade Innate Immunity to Initiate Biofilm Infection on an Implanted Medical Device? (1R56AI155692-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10387835. Licensed CC0.

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