An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.
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 ≤ 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 (>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 antimicrobials and fibrinolytic drugs, particularly during the early stages of device-related infection.
['Zapotoczna|Marta|M|', 'McCarthy|Hannah|H|', 'Rudkin|Justine K|JK|', "O'Gara|James P|JP|", "O'Neill|Eoghan|E|"]
D000328:Adult D000818:Animals D000900:Anti-Bacterial Agents D018441:Biofilms D055499:Catheter-Related Infections D003030:Coagulase D004195:Disease Models, Animal D005343:Fibrinolytic Agents D006801:Humans D017207:Rats, Sprague-Dawley D013211:Staphylococcus aureus
coagulase Staphylococcus biofilm infection antimicrobial susceptibility