Protein Provides Clues to Identifying and Treating Crippling, Costly Bone Infections

Staph (Staphylococcus aureus) is the most common germ to afflict humans, and one of the most damaging: it causes diseases like osteomyelitis (bone infection), endocarditis (heart inflammation), and skin infections that trigger devastating health consequences, including septic shock and death.

Efforts to find a way to spot and treat staph infections early have failed so far, but in a paper published in mBio, researchers at the University of Rochester School of Medicine & Dentistry believe they’ve found answers in a small protein known as a chemokine.

Chemokines attract immune cells to a site of infection or injury. The team studied a specific chemokine, CCL20, in staph-induced bone infection in mice. They found a steady, progressive increase in CCL20 levels after infection. Mice lacking CCL20 suffered worse infections and larger abscesses at the infection site, indicating that these substances play a role in the body’s ability to fight infection.

Searching for a Faster Diagnostic Tool

Researchers also noted that CCL20 was present in healthy patients who had undergone a hip or knee replacement without experiencing infection but spiked fivefold in those who got a bone infection and, remarkably, were 100 times the normal level in those who died of sepsis. This suggests that the body uses the chemokine as an SOS signal to the immune system when infection occurs, and that the level of CCL20 could serve as a prognostic biomarker that could signal whether the infection is growing or subsiding via a simple blood test.

“Treating a staph infection quickly offers patients the best chance at recovery and can prevent the risk of sepsis, which can cause death in a matter of hours,” said Gowrishankar Muthukrishnan, PhD, assistant professor in Orthopaedics and Microbiology & Immunology at the University of Rochester’s Center for Musculoskeletal Research. “There is no satisfactory treatment or diagnostic test for bone infection, and there has been no improvement in surgical outcomes in more than 20 years. It would be a huge advantage for surgeons if we could use a simple blood draw to measure CCL20 and predict the patient outcome based on its levels and further help surgeons to add appropriate interventions.”

A Costly, Potentially Deadly Joint Surgery Complication

Approximately 2 million people get total joint replacements in the US annually. It’s generally a very successful surgery, but osteomyelitis is a dreaded post-op complication. Some patients suffer bone loss or need their new joint implant removed and replaced, and some progress to sepsis, an autoimmune crisis that can shut down organs and lead to death within hours.

While the number of patients suffering infections is low, the impact of this post-surgical complication is significant. Infections can burrow deep in the bone’s weblike structure and become pernicious, so patients may require months-long courses of antibiotics. Once a patient is infected, the rate of reinfection is almost 50 percent.

The current health care burden from bone infection is significant and rapidly growing. With the aging population and the increasing number of joint replacement surgeries, it’s estimated there will be up to 200,000 prosthetic joint infections annually by 2030, and total associated healthcare costs for bone infection are projected to reach $3 billion a year in that timeframe.

According to first author Himanshu Meghwani, PhD, staff scientist at the Center for Musculoskeletal Research, CCL20 could potentially be useful as an anti-infection therapy. Because it recruits immune cells to an infection site, it may enhance the body’s infection-fighting response. But researchers have more to learn; their study showed that some patients, despite a dramatic CCL20 presence, fail to fight off infection and enter into sepsis.

The study was funded by the National Institutes of Health with additional funding from the AOTrauma Clinical Priority Program, Lupus Research Alliance, and the AAI Careers in Immunology Fellowship Program. Co-authors of the paper include Jennifer H. Jonason, PhD, and Edward Schwarz, PhD, of the Center for Musculoskeletal Research at the University of Rochester, and Stephen L. Kates from the department of Orthopaedics at Virginia Commonwealth University.