title: Plasminogen is a critical host pathogenicity factor for group A streptococcal infection.
abstract: Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Sun
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ringdahl
authors.forename: Jonathon W
authors.initials: JW
authors.lastname: Homeister
authors.forename: William P
authors.initials: WP
authors.lastname: Fay
authors.forename: N Cary
authors.initials: NC
authors.lastname: Engleberg
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Yang
authors.forename: Laura S
authors.initials: LS
authors.lastname: Rozek
authors.forename: Xixi
authors.initials: X
authors.lastname: Wang
authors.forename: Ulf
authors.initials: U
authors.lastname: Sjöbring
authors.forename: David
authors.initials: D
authors.lastname: Ginsburg
mesh_terms: D000721:Ancrod / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D017353:Gene Deletion; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000382:microbiology; D013045:Species Specificity; D013154:Spleen / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D013300:Streptokinase / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D014774:Virulence
chemical_list: D000925:Anticoagulants; D001426:Bacterial Proteins; D002352:Carrier Proteins; C084529:plasminogen-binding protein, bacteria; D005337:Fibrin; D010958:Plasminogen; D013300:Streptokinase; D000721:Ancrod; D005341:Fibrinolysin