title: CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates blood coagulation.
abstract: Acinetobacter baumannii is an important nosocomial pathogen that displays high antibiotic resistance. It causes a variety of infections including pneumonias and sepsis which may result in disseminated intravascular coagulation. In this work, we identify and characterize a novel secreted, zinc-dependent, metallo-endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter baumannii) which deregulates human blood coagulation in vitro and thus is likely to contribute to A. baumannii virulence. Three quarters of the clinical isolates tested (n = 16) had the cpaA gene; however, it was absent from two type strains, A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was purified from one clinical isolate and was able to cleave purified factor (F) V and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA-treated plasma showed reduced clotting activity in contact pathway-activated partial thromboplastin time (aPTT) assays, but increased clotting activity in tissue factor pathway prothrombin time (PT) assays. A significant portion of clinically relevant A. baumannii isolates secrete a protease which targets and deregulates the coagulation system.
authors.affiliation: Centennial College, School of Engineering Technology and Applied Science, Toronto, ON, Canada; CancerControl, Alberta Health Services, Richmond Road Diagnostic & Treatment Centre, Calgary, AB, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Tilley
authors.forename: Robert
authors.initials: R
authors.lastname: Law
authors.forename: Sarah
authors.initials: S
authors.lastname: Warren
authors.forename: John A
authors.initials: JA
authors.lastname: Samis
authors.forename: Ayush
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000151:Acinetobacter Infections / Q000097:blood* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000201:enzymology* / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D001777:Blood Coagulation; D020134:Catalytic Domain; D017124:Conserved Sequence; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000502:physiology*; D010314:Partial Thromboplastin Time; D059748:Proteolysis; D020539:Sequence Analysis, Protein
chemical_list: D001426:Bacterial Proteins; D005340:Fibrinogen; D008666:Metalloendopeptidases
keywords: bacterial infection; blood clot; factor V; fibrinogen; virulence factor