Cell Host & Microbe Previews Staphylococcus aureus Osteomyelitis : Bad to the Bone

Osteomyelitis is a bacterial infection of the bone or bone marrow that affects an alarming number of patients that are admitted to hospitals (Lew and Waldvogel, 2004). Staphylococcus aureus is a prominent bacterial pathogen and the most frequent isolated causal agent of infection-induced osteomyelitis (Hatzenbuehler and Pulling, 2011). Treatment of osteomyelitis infections is challenging due a variety of factors including the poor bioavailability of antibiotics in bone tissue, rising antibiotic resistance in bacterial pathogens, and the biofilm-like properties of the infection. In many cases, physicians are left with surgical debridement as the only option to remove the invading bacteria and achieve a sterile site. When an infected prosthetic joint is involved, removal and replacement of the joint is often required (Zimmerli et al., 2004). Due to these challenges, osteomyelitis is devastating formany patients, with painful long-term consequences and limited treatment options. Improving the clinical outcomes of osteomyelitis infections would be a significant medical advance. Our current limited knowledge of disease progression and the availability of technologies to monitor these events is an unmet need that has hampered ongoing studies. In this issue of Cell Host & Microbe, Cassat et al. (2013) address these challenges by developing and utilizing a novel threedimensional imaging modality called high-resolution microcomputed tomography (microCT) that can visualize and quantify infectious damage to the bone. To perform microCT, a new model of murine osteomyelitis was developed and confirmed using a community-acquired methicillin-resistant S. aureus isolate of the USA300 type, an emerging cause of musculoskeletal infections (Kourbatova et al., 2005). In the murine model, a sterile 1 mm unicortical bone defect is created, serving as an S. aureus inoculation point to establish osteomyelitis. To monitor disease progression, microCT is performed to visualize cortical bone destruction and new bone formation, and computational algorithms translate these changes into a three-dimensional image. The end result is a visual reconstruction that captures a striking snapshot of bone remodeling as a result of S. aureus infection (see Figure 1). The developed imaging software provides informative volume outputs of bone loss and new bone growth that serve an important role in quantifying osteomyelitis-related damage. To verify the microCT findings, the authors (Cassat et al., 2013) performed histopathology on the murine model. Thus, the methods developed in this paper make it possible to monitor and quantify osteomyelitis disease for the first time using a powerful new imaging platform. To gain insight into S. aureus mechanisms of osteomyelitis pathogenesis, Cassat et al. (2013) employed themicroCT imaging technology on USA300 and isogenic mutants in previously described key pathogenesis regulators. Due to the limited knowledge of contributing factors to this disease, a S. aureus strain lacking two global virulence regulators (Agr and Sae systems) was tested in the murinemodel. The doublemutant showed significantly less cortical bone destruction and reduced new bone formation, indicating that secreted virulence factors were likely critical contributors to disease. To focus the subsequent studies, single mutants were tested, and a sae mutant