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

Kastrup, Christian J. and Boedicker, James Q. and Pomerantsev, Andrei P. and Moayeri, Mahtab and Bian, Yao and Pompano, Rebecca R. and Kline, Timothy R. and Sylvestre, Patricia and Shen, Feng and Leppla, Stephen H. and Tang, Wei-Jen and Ismagilov, Rustem F. (2008) Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting'. Nature Chemical Biology, 4 (12). pp. 742-750. ISSN 1552-4450.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle Information
Shen, Feng0000-0002-4709-330X
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:© 2008 Nature Publishing Group. Received 7 May 2008; Accepted 8 October 2008; Published online 2 November 2008. This work was supported in part by the US National Institutes of Health (NIH) Director's Pioneer Award (grant number DP1OD003584), the US National Science Foundation CAREER Award (grant number CHE-0349034), the US Office of Naval Research (grant number N000140610630), the Camille Dreyfus Teacher-Scholar Awards Program and the Cottrell Scholar of Research Corporation Awards Program to R.F.I., by NIH grants (GM 62548 and GM 81539) to W.-J.T., and by the Intramural Research Program of the NIAID. We thank J. Alverdy, B. Bishop, S. Crosson, C. Esmon, M. Mock, M. Runyon, J. Shapiro, U. Spitz, T. Van Ha, D. Wiebel and O. Zaborina for helpful discussions; O. Zaborina (The University of Chicago) for the gift of the EGPF plasmid for E. coli and for assisting in the transformation procedure; M. Mock (Institut Pasteur) for the gift of the mouse anti-InhA1 serum; L. Cheng and D. Crown for assisting in the animal studies; H. Herwald (Lund University) for the gift of the E. coli Ymel-1 strain; J. Handelsman (University of Wisconsin) for the gift of the B. cereus GFP strain; M. Blaser (New York University) for the gift of the B. anthracis DeltaluxS strain; and J. Price for contributions in writing and editing this manuscript. We thank C. Tallant (Institut de Biologia Molecular de Barcelona) for assistance in construction of the protease gene knockout strains. 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.
Funding AgencyGrant Number
NIH Director’s Pioneer Award1DP1 OD003584
Camille and Henry Dreyfus FoundationUNSPECIFIED
Cottrell Scholar of Research CorporationUNSPECIFIED
NIHGM 62548
NIHGM 81539
Intramural Research Program of the NIAIDUNSPECIFIED
Issue or Number:12
Record Number:CaltechAUTHORS:20130821-160720712
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:40805
Deposited By: Whitney Barlow
Deposited On:27 Aug 2013 19:53
Last Modified:09 Mar 2020 13:19

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