Osteomyelitis is a debilitating bone infection most frequently caused by Staphylococcus aureus ("staph") bacteria. It is particularly challenging to treat.
Now, Vanderbilt microbiologist Eric Skaar, Ph.D., MPH, and colleagues have identified a staph-killing compound that may be an effective treatment for osteomyelitis, and they have developed a new mouse model that will be useful for testing this compound and for generating additional therapeutic strategies.
AdvertisementJames Cassat, M.D., Ph.D., a fellow in Pediatric Infectious Diseases who is interested in improving treatments for children with bone infections, led the mouse model studies. Working with colleagues in the Vanderbilt Center for Bone Biology and the Vanderbilt University Institute of Imaging Science, Cassat developed micro-computed tomography (micro-CT) imaging technologies to visualize a surgically introduced bone infection in progress.
"The micro-CT gives excellent resolution images of the damage that's being done to the bone," said Skaar, the Ernest W. Goodpasture Professor of Pathology. "We found that staph is not only destroying bone, but it's also promoting new bone growth. Staph is causing profound changes in bone remodeling."
Cassat also established methods for recovering - and counting - bacteria from the infected bone.
"We're not aware of any other bone infection models where you can pull the bacteria out of a bone and count them in a highly reproducible manner," Skaar said. "From a therapeutic development standpoint, we think this model is going to allow investigators to test new compounds for efficacy against bone infections caused by staph or any other bacteria that cause osteomyelitis."
Several pharmaceutical companies have already approached Skaar and his team about testing compounds in the new bone infection model, which the investigators describe in the June 12 issue of Cell Host & Microbe.
Using the model, the team demonstrated that a certain protein secreted by staph plays a critical role in the pathogenesis of osteomyelitis. Understanding the specific bacterial factors - and the bone cell signals - that promote bone destruction and formation during infection could lead to new strategies for restoring bone balance, Skaar said.
"Even if it's not possible to kill the bacteria, compounds that manipulate bone growth or destruction might have some therapeutic benefit."