A Novel Mouse Model of Staphylococcus aureus Chronic Osteomyelitis That Closely Mimics the Human Infection: An Integrated View of Disease Pathogenesis

• Published in: The American journal of pathology Vol. 181; no. 4; pp. 1206 - 1214
• Main Authors: HORST, Sarah A, HOERR, Verena, RASCHKE, Michael J, ROHDE, Manfred, PETERS, Georg, FABER, Cornelius, LÖFFLER, Bettina, MEDINA, Eva, BEINEKE, Andreas, KREIS, Carolin, TUCHSCHERR, Lorena, KALINKA, Julia, LEHNE, Sabine, SCHLEICHER, Ina, KÖHLER, Gabriele, FUCHS, Thomas
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Investigative Pathology 01.10.2012
• Subjects: Animals; Bacterial arthritis and osteitis; Bacterial diseases; Biological and medical sciences; Biomechanical Phenomena; Chronic Disease; Disease Models, Animal; Disease Progression; Female; Human bacterial diseases; Humans; Humerus - diagnostic imaging; Humerus - microbiology; Humerus - pathology; Imaging, Three-Dimensional; Infectious diseases; Inflammation - pathology; Investigative techniques, diagnostic techniques (general aspects); Magnetic Resonance Imaging; Medical sciences; Mice; Mice, Inbred C57BL; Osteomyelitis - microbiology; Osteomyelitis - pathology; Osteomyelitis - physiopathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Radiography; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcal Infections - physiopathology; Staphylococcus aureus - physiology; Tibia - diagnostic imaging; Tibia - microbiology; Tibia - pathology; Tibia - ultrastructure; Time Factors; Human; Animal model; Mimic; Pathogenesis; Diseases of the osteoarticular system; Rodentia; Infection; Vertebrata; Anatomic pathology; Chronic; Mammalia; Mouse; Osteitis; Bacteria; Micrococcales; Micrococcaceae; Staphylococcus aureus
• ISSN: 0002-9440; 1525-2191; 1525-2191
• DOI: 10.1016/j.ajpath.2012.07.005

Osteomyelitis is a serious bone infection typically caused by Staphylococcus aureus. The pathogenesis of osteomyelitis remains poorly understood, mainly for lack of experimental models that closely mimic human disease. We describe a novel murine model of metastatic chronic osteomyelitis initiated after intravenous inoculation of S. aureus microorganisms. The bacteria entered bones through the bloodstream and, after an acute phase with progressive growth (first 2 weeks after infection), they remained at constant numbers for up to 56 days (chronic phase). Clinical signs of illness and systemic inflammation were apparent only during the acute phase. Bone destruction and remodeling processes were readily detectable by magnetic resonance and X-ray imaging 3 weeks after infection, and high levels of bone deformation were observed during the chronic phase. Histological examination of infected bones demonstrated suppurative inflammation with foci of intense bacterial multiplication and necrosis during acute infection and osteoclastic resorption accompanied by new woven bone formation during chronic infection. Transmission electron microscopy revealed S. aureus microorganisms forming microcolonies within the nonmineralized collagen matrix or located intracellularly within neutrophils. In summary, our mouse model of staphylococcal hematogenous osteomyelitis precisely reproduces most features of the human disease. Although the extent of lesions in the chronic phase was subject to variation, this model is ideal for testing and monitoring novel treatment modalities via noninvasive imaging.