Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'.
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.
Kastrup
Christian J
CJ
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Boedicker
James Q
JQ
Pomerantsev
Andrei P
AP
Moayeri
Mahtab
M
Bian
Yao
Y
Pompano
Rebecca R
RR
Kline
Timothy R
TR
Sylvestre
Patricia
P
Shen
Feng
F
Leppla
Stephen H
SH
Tang
Wei-Jen
WJ
Ismagilov
Rustem F
RF
D000818:Animals; D001408:Bacillus anthracis; D001409:Bacillus cereus; D001424:Bacterial Infections / Q000150:complications*; D018407:Bacterial Physiological Phenomena; D001777:Blood Coagulation; D005170:Factor X; D006801:Humans; D045726:Metalloproteases; D051379:Mice; D044085:Microfluidics; D008954:Models, Biological; D011516:Prothrombin; D053038:Quorum Sensing
D011516:Prothrombin; D005170:Factor X; D045726:Metalloproteases