New research from the Royal College of Surgeons in Ireland (RCSI) has identified a novel drug target for the treatment of infection in bone. The research was recently published in the journal PLoS ONE* and won the Donegan Bronze Medal at the annual meeting of the Biomedical section of the Royal Academy of Medicine in Ireland.
Bone disease or Osteomyeltitis is a debilitating infectious disease of the bone which is associated with significant morbidity and mortality. It is characterised by severe inflammation and progressive bone destruction and is usually caused by the bacterium Staphylococcus aureus that lives commonly on human skin and in the nose. It can reach the bones through blood contamination, open wounds or during surgery and most often causes infections in people with compromised immune systems.
Dr. Steve Kerrigan, lead researcher said "Our findings identify the exact mechanism through which Staphylococcus aureus binds to bone cells and triggers their destruction. It appears that Staphylococcus aureus can bind to bone cells and force them to undergo programmed cell death or apoptosis. When this occurs bone cells die and do not rejuvenate themselves. This leads to severe weakening of the bone, increasing the risk of multiple fractures in these patients. Deletion of specific protein on Staphylococcus aureus that binds to bone cells prevents the death signal, thus making it an ideal candidate as a novel drug target and prevents our over-reliance on antibiotics to treat this disease."
Current treatment guidelines consist of aggressive prolonged antibiotic therapy, possibly combined with surgery. Prolonged antibiotic use is often less than successful as 40% of patients relapse within 2 months of finishing clinically effective therapy. Furthermore, prolonged exposure to antibiotics leads to a greater risk of adding to the global problem of multiple antibiotic resistant strains of bacteria.
Bone disease, or osteomyelitis, affects 1 in 5,000 people around the world. It can occur at any stage in life and attack any bone in the body, where it leads to progressive bone destruction.
The research is a result of a successful collaborative project carried out between the Host Infection Group led by Dr. Steve Kerrigan in the School of Pharmacy and Molecular and Cellular Therapeutics and the Tissue Engineering Research Group led by Prof Fergal O'Brien in the Department of Anatomy. This research was funded by the Science Foundation of Ireland Research Frontiers Programme.
- Tania Claro, Amro Widaa, Maghnus O'Seaghdha, Helen Miajlovic, Timothy J. Foster, Fergal J. O'Brien, Steven W. Kerrigan. Staphylococcus aureus Protein A Binds to Osteoblasts and Triggers Signals That Weaken Bone in Osteomyelitis. PLoS ONE, 2011; 6 (4): e18748 DOI: 10.1371/journal.pone.0018748
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