An essential role for coagulase instaphylococcus aureusbiofilm development reveals new therapeutic possibilities for device-related infections
Rudkin, Justine K.
O'Gara, James P.
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Zapotoczna, Marta; McCarthy, Hannah; Rudkin, Justine K. O'Gara, James P.; O'Neill, Eoghan (2015). An essential role for coagulase instaphylococcus aureusbiofilm development reveals new therapeutic possibilities for device-related infections. Journal of Infectious Diseases 212 (12), 1883-1893
High-level resistance to antimicrobial drugs is a major factor in the pathogenesis of chronic Staphylococcus aureus biofilm-associated, medical device-related infections. Antimicrobial susceptibility analysis revealed that biofilms grown for &lt;= 24 hours on biomaterials conditioned with human plasma under venous shear in iron-free cell culture medium were significantly more susceptible to antistaphylococcal antibiotics. Biofilms formed under these physiologically relevant conditions were regulated by SaeRS and dependent on coagulase-catalyzed conversion of fibrinogen into fibrin. In contrast, SarA-regulated biofilms formed on uncoated polystyrene in nutrient-rich bacteriological medium were mediated by the previously characterized biofilm factors poly-N-acetyl glucosamine, fibronectin-binding proteins, or autolytic activity and were antibiotic resistant. Coagulase-mediated biofilms exhibited increased antimicrobial resistance over time (&gt;48 hours) but were always susceptible to dispersal by the fibrinolytic enzymes plasmin or nattokinase. Biofilms recovered from infected central venous catheters in a rat model of device-related infection were dispersed by nattokinase, supporting the important role of the biofilm phenotype and identifying a potentially new therapeutic approach with anti-microbials and fibrinolytic drugs, particularly during the early stages of device-related infection.