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

Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Nature Chemical Biology (Impact Factor: 13.22). 01/2009; 4(12):742-50. DOI: 10.1038/nchembio.124
Source: PubMed

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.


Available from: Andrei P Pomerantsev, Jun 03, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a number of experimental studies, it has been demonstrated that the forefront of blood coagulation can propagate in the manner of a signal relay. These data strongly support the concept that the formation of a blood clot is governed by a self-sustained traveling wave of thrombin. The present review critically appraises the experimental data obtained in recent decades concerning the self-sustained spatial propagation of thrombin. Open questions regarding the experimental detection of the self-sustained propagation of thrombin are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 12/2014; 135(3). DOI:10.1016/j.thromres.2014.12.014 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role, hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with virtually all known immune cells. These platelet-immune cell interactions are a hallmark of immunity as they can potently enhance immune cell functions and in some cases even constitute a prerequisite for host defense mechanisms like NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first line immune responders as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells and provide an exemplary review of their role to acute inflammation in acute lung injury.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 09/2014; 12(11). DOI:10.1111/jth.12730 · 5.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Catheter-related bloodstream infections (CRBSIs) and catheter-related thrombosis (CRT) are common complications of central venous catheters (CVC), which are used to monitor patient health and deliver medications. CVCs are subject to protein adsorption and platelet adhesion as well as colonization by the natural skin flora (i.e. Staphylococcus aureus and Staphylococcus epidermidis). Antimicrobial and antithrombotic drugs can prevent infections and thrombosis-related complications, but have associated resistance and safety risks. Surface topographies have shown promise in limiting platelet and bacterial adhesion, so it was hypothesized that an engineered Sharklet micropattern, inspired by shark-skin, may provide a combined approach as it has wide reaching anti-fouling capabilities. To assess the feasibility for this micropattern to improve CVC-related healthcare outcomes, bacterial colonization and platelet interactions were analyzed in vitro on a material common for vascular access devices. To evaluate bacterial inhibition after simulated vascular exposure, micropatterned thermoplastic polyurethane surfaces were preconditioned with blood proteins in vitro then subjected to a bacterial challenge for 1 and 18 h. Platelet adhesion was assessed with fluorescent microscopy after incubation of the surfaces with platelet-rich plasma (PRP) supplemented with calcium. Platelet activation was further assessed by monitoring fibrin formation with fluorescent microscopy after exposure of the surfaces to platelet-rich plasma (PRP) supplemented with calcium in a flow-cell. Results are reported as percent reductions and significance is based on t-tests and ANOVA models of log reductions. All experiments were replicated at least three times. Blood and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S. epidermidis colonization by 70% (p ≤ 0.05) and 71% (p < 0.01), respectively, when compared to preconditioned unpatterned controls. Additionally, platelet adhesion and fibrin sheath formation were reduced by 86% and 80% (p < 0.05), respectively, on the micropattern, when compared to controls. The Sharklet micropattern, in a CVC-relevant thermoplastic polyurethane, significantly reduced bacterial colonization and relevant platelet interactions after simulated vascular exposure. These results suggest that the incorporation of the Sharklet micropattern on the surface of a CVC may inhibit the initial events that lead to CRBSI and CRT.
    12/2015; 4(1):9. DOI:10.1186/s40169-015-0050-9