Structural Basis for Reduced Staphylocoagulase-mediated Bovine Prothrombin Activation

Friedrich, Rainer W.; Panizzi, Peter; Kawabata, Shun Ichiro; Bode, Wolfram; Bock, Paul E.; Fuentes‐Prior, Pablo

doi:10.1074/jbc.m507957200

Cited by 21 publications

(19 citation statements)

References 32 publications

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“…S2), which is consistent with the existence of the host specific SaPI‐carried paralogues of the vWbp. Prothrombin activation by either protein occurs by the newly described ‘sexual’ activation mechanism where a specific short N‐terminal amino acid segment of the activator (‘male’) physically inserts into a cleft in the receptor (prothrombin) molecule (female) (Friedrich et al ., 2006; Kroh et al ., 2009). As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Either coagulase or vWbp, or both could be involved in animal specificity. Since all S. aureus strains produce coagulase, which does not effectively induce clotting of ruminant plasma (Friedrich et al ., 2006), we have addressed the possibility that vWbp may be the putative clotting factor involved in animal adaptation. We report here that S. aureus strains isolated from ruminants and horses, but not from most other animals, encode vWbp paralogues, carried by mobile pathogenicity islands (SaPIs), which are specific for ruminant or equine plasma.…”

Section: Introductionmentioning

confidence: 99%

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Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI‐carried variants of von Willebrand factor‐binding protein

Martín

Blanco

Tormo-Más

et al. 2010

Molecular Microbiology

143

134

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SummaryStaphylococci adapt specifically to various animal hosts by genetically determined mechanisms that are not well understood. One such adaptation involves the ability to coagulate host plasma, by which strains isolated from ruminants or horses can be differentiated from closely related human strains. Here, we report first that this differential coagulation activity is due to animal-specific alleles of the von Willebrand factor-binding protein (vWbp) gene, vwb, and second that these vwb alleles are carried by highly mobile pathogenicity islands, SaPIs. Although all Staphylococcus aureus possess chromosomal vwb as well as coagulase (coa) genes, neither confers speciesspecific coagulation activity; however, the SaPIcoded vWbps possess a unique N-terminal region specific for the activation of ruminant and equine prothrombin. vWbp-encoding SaPIs are widely distributed among S. aureus strains infecting ruminant or equine hosts, and we have identified and characterized four of these, SaPIbov4, SaPIbov5, SaPIeq1 and SaPIov2, which encode vWbp Sbo4, vWbp Sbo5, vWbp Seq1 and vWbp Sov2 respectively. Moreover, the SaPI-carried vwb genes are regulated differently from the chromosomal vwb genes of the same strains. We suggest that the SaPI-encoded vWbps may represent an important host adaptation mechanism for S. aureus pathogenicity, and therefore that acquisition of vWbp-encoding SaPIs may be determinative for animal specificity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI‐carried variants of von Willebrand factor‐binding protein

Martín

Blanco

Tormo-Más

et al. 2010

Molecular Microbiology

143

134

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“…These bacterial components usually activate low levels of coagulation factors, which does not result in the amplification and positive feedback necessary to form a clot that can grow and propagate. For example, Staphylococcus aureus produces coagulase, a protein that binds prothrombin stoichiometrically and leads to cleavage of fibrinogen to fibrin14. However, this conversion simply precipitates fibrin and does not result in production of thrombin, feedback or amplification of the coagulation cascade.…”

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confidence: 99%

Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'

et al. 2008

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Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as 'quorum acting' to distinguish it from quorum sensing-it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication.This paper describes a physical and biochemical mechanism responsible for regulating the initiation of human blood coagulation by bacteria. In vivo, coagulation often accompanies bacterial infections of the blood and is believed to be a consequence of immune and inflammatory responses 1-5 . Immune and inflammatory responses cause upregulation of tissue factor on the timescale of hours and lead to increased coagulation 6,7 . One of the few drugs available to treat septic shock, activated protein C, is also an anticoagulant 8 . This coagulation is believed to prevent dissemination of bacteria through the blood 9,10 but also results in serious vascular damage due to blockage and injury of blood vessels 8 . Coagulation accompanying bacterial infections of the blood is particularly relevant for people infected with anthrax, which involves sepsis and disseminated intravascular coagulation caused by the pathogen Bacillus Correspondence should be addressed to R.F.I. (r-ismagilov@uchicago.edu).. AUTHOR CONTRIBUTIONS C.J.K., J.Q.B., M.M., Y.B., R.R.P., T.R.K. and F.S. performed experiments; C.J.K., J.Q.B., M.M., Y.B., R.R.P., T.R.K., F.S., S.H.L., W.-J.T. and R.F.I. designed experiments and analyzed data; C.J.K., W.-J.T. and R.F.I. wrote the paper; A.P.P. and P.S. provided reagents. NIH Public Access Author ManuscriptNat Chem Biol. Author manuscript; available in PMC 2009 June 1. Published in final edited form as:Nat Chem Biol. 2008 December ; 4(12): 742-750. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript anthracis 4 . Here, we considered an alternative and complementary mechanism for the coagulation that accompanies infection: direct activation of the human coagulation cascade through activation of coagulation factors by bacteria.Many bacteria and bacterial components can directly activate individual human coagulation factors. However, direct initiation of the coagulation cascade and the formation of a propagating clot are not typically observed 11-17 ...

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“…1 shows an alignment of the crystallographically defined 1-281 sequence of SC from strain Tager 104, compared with sequences of SCs from different bacterial strains, which are representative of the distinct SC variants of S. aureus. In the SC-(1-325)⅐Pre 2 complex, each SC molecule consists of two independent, rod-like helical domains, D1 and D2 (3,34). The three-helix bundle of D2 covers the basic anion binding exosite I located to the "east" of the thrombin active site.…”

Section: Molecular Weights Of Sc-(1-325) and Sc-(1-325)⅐prethrombin 1mentioning

confidence: 99%

“…2) Recently, a crystal structure of Fbg fragment E bound to human thrombin was presented, which shows that the substrate primarily contacts residues of the 37 (e.g. Phe 34 and Ser 36A ), and 70 -80 loops (Tyr 76 and Arg 77A ) (36). Surprisingly, SC domain D2 not only overlaps but turns out to bury a larger area of thrombin exosite I than the substrate Fbg (1,560 Å 2 compared with Ͻ1,200 Å 2 ).…”

Section: Molecular Weights Of Sc-(1-325) and Sc-(1-325)⅐prethrombin 1mentioning

confidence: 99%

Fibrinogen Substrate Recognition by Staphylocoagulase·(Pro)thrombin Complexes

Panizzi

Friedrich

Fuentes‐Prior

et al. 2006

Journal of Biological Chemistry

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Structural Basis for Reduced Staphylocoagulase-mediated Bovine Prothrombin Activation

Cited by 21 publications

References 32 publications

Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI‐carried variants of von Willebrand factor‐binding protein

Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI‐carried variants of von Willebrand factor‐binding protein

Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'

Fibrinogen Substrate Recognition by Staphylocoagulase·(Pro)thrombin Complexes

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