Project Details
Projekt
Analysis of intracellular Staphylococcus aureus and associated bone destruction in chronic osteomyelitis with potential new anti-inflammatory treatment options
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 547933897
Osteomyelitis is the most prevalent musculoskeletal infection in the clinics resulting from hematogenous infection or inoculation of bacteria due to surgery or open fractures. Planktonic or biofilm-forming S. aureus is assumed to affect clinical outcomes. However, during the past years, it became evident that S. aureus also persists intracellularly i.e. in osteoblasts. The clinical relevance of intracellular S. aureus has not been clarified to date. We hypothesize that intracellular trafficking and proliferation of bacteria and the associated inflammatory processes in osteoblasts contribute to the altered bone metabolism and bone remodeling observed during chronic osteomyelitis. We will address the underlying mechanisms of bacterial uptake, intracellular trafficking, and resulting remodeling of the host cell in a model cell line. We will apply state-of-the-art biochemical, cell, and molecular biological techniques, subcellular cellular fractionation, and omics approaches scrutinizing the transcriptome, proteome, and lipidome of infected cells in detail. The observations will be validated in patient-derived material and based on this, possible novel therapeutic strategies will be tested, which target bacterial proliferation and inflammatory host response. We will validate putative novel biomarkers and therapeutic targets, and analyze the current medication to possibly derive novel therapeutic options for the treatment of osteomyelitis in the future.
DFG Programme
Research Grants
