# Center of Research Translation on the Osteoimmunology of Bone Infection

> **NIH NIH P50** · UNIVERSITY OF ROCHESTER · 2021 · $1,140,009

## Abstract

Abstract
 Prosthetic joint infection (PJI) is the bane of elective total joint replacement (TJR) surgery, of
which the vast majority is caused by Staphylococcal species. Although the number of primary infections
following TJR is low (1-5%), reinfection rates are very high (15-40%), which has led to the orthopaedic
paradigm that S. aureus infection of bone is incurable. Additionally, PJI is known to be a non-random
event that is largely determine by patient-specific factors, as infections are caused by only a few
prevalent nosocomial strains (i.e. MRSA USA300), and implementation of the most rigorous surgical
systems is incapable of reducing infection rates below 1%. Moreover, ~13% of patients infected with S.
aureus become septic and die from multiorgan failure, while others recover with little intervention. To
address these very significant issues, we propose the Center of Research Translation on the
Osteoimmunology of Bone Infection (CoRTOBI), which is the evolution of two highly successful
programs (AOTrauma Clinical Priority Program on Bone Infection (AO-CPP); and NIAMS P50 CORT
AR54041 “Translating Molecular Signal Pathways to Orthopaedic Trauma Care”) that will be completed
this year. To capitalize on the salient strengths of these programs, the CoRTOBI now proposes to
advance and translate the major discoveries from the AO-CPP on S. aureus infection of bone and host
immunity, using the proven administrative structure of the P50 CORT. These discoveries include: 1) S.
aureus colonization of the osteocytic-canalicular network of live bone, 2) novel antibiotics that
specifically target these mechanisms, which can be 3D-printed into custom spacers, 3) development of
a custom multiplex Luminex assay to elucidate the immune proteome of S. aureus, and 4) identification
of the anti-Isd vs. anti-Atl immune proteome ratio as a susceptible vs. protective index of host immunity
against S. aureus. The proposed CoRTOBI will consist of an Administrative Core that will provide
operational and fiscal management of the CoRTOBI, as well as a Clinical Research Sub-Core, a
Biostatistics Sub-Core, an Enrichment Programs, and a Pilot and Feasibility Project Program. There are
two Research Projects. Project 1 is focused on elucidating the mechanisms of S. aureus motility in
bone and developing novel antibiotic impregnated 3D-printed spacers. Project 2 is focused on defining
the susceptible vs. protective immune proteomes of Staphylococcus osteomyelitis and interventions for
septic death. The Projects will be supported by an Osteoimmunology Research Core, which will
provide state of the art imaging, biomaterial fabrication and immunoassay analyses. At the conclusion
of this CoRTOBI we will have new knowledge on the microbial pathogenesis of bone infection and the
host response. We will also develop novel diagnostics and interventions for patients with osteomyelitis.

## Key facts

- **NIH application ID:** 10247748
- **Project number:** 5P50AR072000-05
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Edward M. Schwarz
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,140,009
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247748

## Citation

> US National Institutes of Health, RePORTER application 10247748, Center of Research Translation on the Osteoimmunology of Bone Infection (5P50AR072000-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247748. Licensed CC0.

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