Abstract
Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-xL, an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-xL protein in platelets. Bcl-xL protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the poreforming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-xL protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-xL protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.
| Original language | English |
|---|---|
| Pages (from-to) | 5014-5020 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 120 |
| Issue number | 25 |
| DOIs | |
| State | Published - Dec 13 2012 |
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Kraemer, B. F., Campbell, R. A., Schwertz, H., Franks, Z. G., De Abreu, A. V., Grundler, K., Kile, B. T., Dhakal, B. K., Rondina, M. T., Kahr, W. H. A., Mulvey, M. A., Blaylock, R. C., Zimmerman, G. A., & Weyrich, A. S. (2012). Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets. Blood, 120(25), 5014-5020. https://doi.org/10.1182/blood-2012-04-420661
Kraemer, Bjoern F. ; Campbell, Robert A. ; Schwertz, Hansjörg et al. / Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets. In: Blood. 2012 ; Vol. 120, No. 25. pp. 5014-5020.
@article{77892fb7ab0f425db9b407fc1e10310e,
title = "Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets",
abstract = "Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-xL, an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-xL protein in platelets. Bcl-xL protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the poreforming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-xL protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-xL protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.",
author = "Kraemer, {Bjoern F.} and Campbell, {Robert A.} and Hansj{\"o}rg Schwertz and Franks, {Zechariah G.} and {De Abreu}, {Adriana Vieira} and Katharina Grundler and Kile, {Benjamin T.} and Dhakal, {Bijaya K.} and Rondina, {Matthew T.} and Kahr, {Walter H.A.} and Mulvey, {Matthew A.} and Blaylock, {Robert C.} and Zimmerman, {Guy A.} and Weyrich, {Andrew S.}",
year = "2012",
month = dec,
day = "13",
doi = "10.1182/blood-2012-04-420661",
language = "English",
volume = "120",
pages = "5014--5020",
journal = "Blood",
issn = "0006-4971",
number = "25",
}
Kraemer, BF, Campbell, RA, Schwertz, H, Franks, ZG, De Abreu, AV, Grundler, K, Kile, BT, Dhakal, BK, Rondina, MT, Kahr, WHA, Mulvey, MA, Blaylock, RC, Zimmerman, GA & Weyrich, AS 2012, 'Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets', Blood, vol. 120, no. 25, pp. 5014-5020. https://doi.org/10.1182/blood-2012-04-420661
Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets. / Kraemer, Bjoern F.; Campbell, Robert A.; Schwertz, Hansjörg et al.
In: Blood, Vol. 120, No. 25, 13.12.2012, p. 5014-5020.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets
AU - Kraemer, Bjoern F.
AU - Campbell, Robert A.
AU - Schwertz, Hansjörg
AU - Franks, Zechariah G.
AU - De Abreu, Adriana Vieira
AU - Grundler, Katharina
AU - Kile, Benjamin T.
AU - Dhakal, Bijaya K.
AU - Rondina, Matthew T.
AU - Kahr, Walter H.A.
AU - Mulvey, Matthew A.
AU - Blaylock, Robert C.
AU - Zimmerman, Guy A.
AU - Weyrich, Andrew S.
PY - 2012/12/13
Y1 - 2012/12/13
N2 - Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-xL, an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-xL protein in platelets. Bcl-xL protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the poreforming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-xL protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-xL protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.
AB - Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-xL, an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-xL protein in platelets. Bcl-xL protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the poreforming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-xL protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-xL protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.
UR - http://www.scopus.com/inward/record.url?scp=84871043440&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-04-420661
DO - 10.1182/blood-2012-04-420661
M3 - Article
C2 - 23086749
AN - SCOPUS:84871043440
SN - 0006-4971
VL - 120
SP - 5014
EP - 5020
JO - Blood
JF - Blood
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ER -
Kraemer BF, Campbell RA, Schwertz H, Franks ZG, De Abreu AV, Grundler K et al. Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets. Blood. 2012 Dec 13;120(25):5014-5020. doi: 10.1182/blood-2012-04-420661
