Article abstract
Nature Chemical Biology 4, 742 - 750 (2008)
Published online: 2 November 2008 | doi:10.1038/nchembio.124
Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'
Christian J Kastrup1, James Q Boedicker1, Andrei P Pomerantsev2, Mahtab Moayeri2, Yao Bian3, Rebecca R Pompano1, Timothy R Kline1, Patricia Sylvestre4,5, Feng Shen1, Stephen H Leppla2, Wei-Jen Tang3 & Rustem F Ismagilov1
Abstract
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.
- Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
- Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 30 Convent Drive, Building 30, Room 303, Bethesda, Maryland 20892-4349, USA.
- Ben-May Institute for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
- Unité Toxines et Pathogénie Bactériennes, Institut Pasteur
- Centre National de la Recherche Scientifique, Unité de Recherche Associée 2172, 28 rue du Dr Roux, 75724 Paris cédex 15, France.
Correspondence to: Rustem F Ismagilov1 e-mail: r-ismagilov@uchicago.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Acting together, bacterial clusters initiate coagulationNature Chemical Biology News and Views (01 Dec 2008)
Switching serine protease specificityNature Structural Biology News and Views (01 Nov 1998)
See all 13 matches for News And ViewsRESEARCH
X-ray structure of antistasin at 1.9 ???? resolution and its modelled complex with blood coagulation factor XaThe EMBO Journal Article (01 Sep 1997)
See all 36 matches for Research
