Activation of inducible nitric oxide synthase/nitric oxide by curli fibers leads to a fall in blood pressure during systemic Escherichia coli infection in mice.
Septic shock, a major cause of death, is characterized by a pathophysiologic increased production of nitric oxide (NO), which leads to vasodilation and myocardial toxicity. Septic Escherichia coli frequently express proteinaceous curli fibers. In this study, curliated E. coli induced high levels of NO by directly inducing type 2 nitric oxide synthase (NOS2) both in vitro and in vivo. More severe hypotension and higher plasma nitrite/nitrate levels were seen in wild type mice systemically infected with curliated E. coli than in animals infected with E. coli mutants that lacked curli proteins. Blood pressure remained stable in NOS2-deficient mice with curliated bacteria. Increased heart rates, transient hypothermia, and loss of gross activity were seen in all mice, regardless of curli expression. Study results suggest that expression of curli fibers by E. coli activates the NO/NOS2 arm of the innate immune system, which leads to a significant fall in blood pressure.
Bian
Z
Z
Microbiology and Tumorbiology Center, NOVUM, Huddinge University Hospital, Karolinska Institute, 141 57, Huddinge, Sweden. zhao.bian@mednut.ki.se
Yan
Z Q
ZQ
Hansson
G K
GK
Thorén
P
P
Normark
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001794:Blood Pressure; D001831:Body Temperature; D002478:Cells, Cultured; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology*; D029968:Escherichia coli Proteins; D006339:Heart Rate; D007022:Hypotension / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000382:microbiology / Q000503:physiopathology
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; C489688:csgA protein, E coli; C077481:Crl protein, Bacteria; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat