# The role of Staphylococcus aureus aggregate formation in establishing biofilms in chronic orthopaedic periprosthetic joint infection.

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $490,778

## Abstract

PROJECT SUMMARY
Periprosthetic joint infection (PJI) after placement of an artificial joint is a devastating complication for both the
patient and surgeon. Infection typically requires an arduous course of repeated surgeries with multiple courses
of broad-spectrum antibiotics administered systemically or locally by antibiotic loaded bone cements. In many
cases the infection cannot be resolved, even though the isolated pathogen is sensitive to the administered
antibiotics, and amputation is not uncommon. Alarmingly a recent study reports that 26% of patients treated for
PJI were dead within 5 years, twice the number of those being replaced for reasons other than infection and
survivorship rates less than those with prostrate, melanoma and breast cancers. Although the infection incidence
in total hip and total knee arthroplasties is relatively low (2.0% and 2.4% respectively), the number of procedures
is forecast to grow exponentially and 15,000 hips and 50,000 knee PJIs are predicted in the US by 2020. Biofilm
formation on the implant components by bacterial pathogens is associated with the intractability of chronic PJIs.
Biofilms are attached communities of bacterial cells living within an extracellular polymeric substances (EPS)
matrix composed of bacterial polymers and host components. Biofilm formation is a mechanism used for
protection, and it confers high levels of tolerance to antibiotics and resistance to host immunity. However
important unanswered clinical questions remain, how do biofilms become established from what is presumably
a small numbers of cells entering the surgical site in the highly controlled environment of the modern OR and
where do biofilms reside in the infected joint? Aggregation (or agglutination in blood) in staphylococci is a known
virulence factor in sepsis but recently it has been shown that aggregates which form rapidly in human synovial
fluid can attach to surfaces to form biofilms. Aggregation also affords rapid biofilm-like tolerance which may
protect the bacteria before they attach to implants and establish mature biofilms. While in vitro models focus on
interaction with single cells almost nothing is known about the kinetics of attachment and growth from
aggregates. In Aim 1 we will determine the kinetics of aggregation in bovine synovial fluid to determine what size
of aggregates are required to confer tolerance to antibiotics and neutrophil uptake. We will also assess the
relative contribution of host factors, bacterial adhesion proteins and EPS components on aggregation kinetics
and the use of surfactants as surgical irrigants to prevent and disperse aggregates. In Aim 2 we will quantify the
attachment rate of aggregates and subsequent biofilm development on different orthopaedic materials under
controlled shear stresses in flow-cell and chemostat models. In Aim 3 we will use a novel agar encasement
culturing method to map and quantify biofilms to specific locations on entire implants from in situ outgrowt...

## Key facts

- **NIH application ID:** 9999614
- **Project number:** 5R01GM124436-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** PAUL STOODLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $490,778
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999614

## Citation

> US National Institutes of Health, RePORTER application 9999614, The role of Staphylococcus aureus aggregate formation in establishing biofilms in chronic orthopaedic periprosthetic joint infection. (5R01GM124436-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999614. Licensed CC0.

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