title: An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.
abstract: 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.
authors.affiliation: Department of Clinical Microbiology, Education and Research Centre, Beaumont Hospital, Royal College of Surgeons in Ireland.
authors.forename: Marta
authors.initials: M
authors.lastname: Zapotoczna
authors.affiliation: Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Hannah
authors.initials: H
authors.lastname: McCarthy
authors.affiliation: Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Justine K
authors.initials: JK
authors.lastname: Rudkin
authors.affiliation: Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Gara
authors.affiliation: Department of Clinical Microbiology, Education and Research Centre, Beaumont Hospital, Royal College of Surgeons in Ireland Department of Microbiology, Connolly Hospital, Dublin.
authors.forename: Eoghan
authors.initials: E
authors.lastname: O'Neill
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D055499:Catheter-Related Infections / Q000382:microbiology* / Q000517:prevention & control; D003030:Coagulase / Q000378:metabolism*; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000378:metabolism*; D006801:Humans; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D003030:Coagulase; D005343:Fibrinolytic Agents
keywords: Staphylococcus; antimicrobial; biofilm; coagulase; infection; susceptibility