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Published on: October 16, 2014
Insights into S. aureus-Induced Bone Deformation in a Mouse Model of Chronic Osteomyelitis Using Fluorescence and
Shibarjun Mandal1, Astrid Tannert1,2, Christina Ebert1,2
1Leibniz Institute of Photonic Technology (Member of Leibniz Health Technologies, Member of the Leibniz Centre for Photonics in Infection Research, LPI), 07745 Jena, Germany.
Abstract:
Osteomyelitis is an infection of the bone that is often difficult to treat and causes a significant healthcare burden. Staphylococcus aureus is the most common pathogen causing osteomyelitis. Osteomyelitis mouse models have been established to gain further insights into the pathogenesis and host response. Here, we use an established S. aureus hematogenous osteomyelitis mouse model to investigate morphological tissue changes and bacterial localization in chronic osteomyelitis with a focus on the pelvis. X-ray imaging was performed to follow the disease progression. Six weeks post infection, when osteomyelitis had manifested itself with a macroscopically visible bone deformation in the pelvis, we used two orthogonal methods, namely fluorescence imaging and label-free Raman spectroscopy, to characterise tissue changes on a microscopic scale and to localise bacteria in different tissue regions. Hematoxylin and eosin as well as Gram staining were performed as a reference method. We could detect all signs of a chronically florid tissue infection with osseous and soft tissue changes as well as with different inflammatory infiltrate patterns. Large lesions dominated in the investigated tissue samples. Bacteria were found to form abscesses and were distributed in high numbers in the lesion, where they could occasionally also be detected intracellularly. In addition, bacteria were found in lower numbers in surrounding muscle tissue and even in lower numbers in trabecular bone tissue. The Raman spectroscopic imaging revealed a metabolic state of the bacteria with reduced activity in agreement with small cell variants found in other studies. In conclusion, we present novel optical methods to characterise bone infections, including inflammatory host tissue reactions and bacterial adaptation.
Insights
This study reveals how Staphylococcus aureus causes chronic osteomyelitis in mice, detailing bone and tissue changes. Novel optical methods effectively mapped bacterial locations and activity within infected bone tissues.
Area of Science:
- Microbiology
- Biomedical Engineering
- Pathology
Background:
- Osteomyelitis, a challenging bone infection, poses a significant health burden.
- Staphylococcus aureus is the primary bacterial agent responsible for most osteomyelitis cases.
- Mouse models are crucial for understanding osteomyelitis pathogenesis and host responses.
Purpose of the Study:
- To investigate morphological tissue changes and bacterial localization in chronic pelvic osteomyelitis using an S. aureus mouse model.
- To apply advanced optical imaging techniques for detailed microscopic analysis of infected bone tissue.
- To characterize bacterial adaptation and metabolic activity within the chronic infection environment.
Main Methods:
- Established a Staphylococcus aureus hematogenous osteomyelitis mouse model, focusing on the pelvis.
- Utilized X-ray imaging to monitor disease progression over six weeks.
- Employed fluorescence imaging and label-free Raman spectroscopy for microscopic tissue characterization and bacterial localization.
- Performed Hematoxylin and eosin and Gram staining as reference methods.
Main Results:
- Detected chronic infection signs including osseous and soft tissue changes with diverse inflammatory patterns.
- Observed large lesions dominated the infected pelvic tissue, with bacteria forming abscesses and present intracellularly.
- Found bacteria in high concentrations within lesions, with lower numbers in surrounding muscle and trabecular bone.
- Raman spectroscopy indicated reduced bacterial metabolic activity, consistent with small cell variants.
Conclusions:
- Novel optical methods, including Raman spectroscopy, can effectively characterize bone infections and inflammatory responses.
- The study provides insights into bacterial localization, adaptation, and metabolic states in chronic osteomyelitis.
- These advanced imaging techniques offer new possibilities for studying bone infections and host-pathogen interactions.
