Expression of and cytokine activation by Escherichia coli curli fibers in human sepsis.
Curli organelles are expressed by commensal Escherichia coli K12 and by Salmonella typhimurium at temperatures <37 degrees C, which bind serum proteins and activate the contact-phase system in vitro. This study demonstrates, by means of an anti-CsgA (curli major subunit) antibody, that a significant fraction of E. coli isolates (24 of 46) from human blood cultures produce curli at 37 degrees C in vitro. Serum samples from 12 convalescent patients with sepsis, but not serum from healthy controls, contained antibodies against CsgA (n=12). This study further demonstrates that a curli-expressing E. coli strain and a noncurliated mutant secreting soluble CsgA induce significantly (P<.05) higher levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, and IL-8) in human macrophages differentiated from THP-1 cells. These data, therefore, provide direct evidence that curli are expressed in vivo in human sepsis and suggest a possible role for curli and CsgA in the induction of proinflammatory cytokines during E. coli sepsis.
Bian
Z
Z
Microbiology and Tumorbiology Center, Karolinska Institute, 171 77 Stockholm, Sweden. zhao.bian@mtc.ki.se
Brauner
A
A
Li
Y
Y
Normark
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003224:Congo Red / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology*; D029968:Escherichia coli Proteins; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008262:Macrophage Activation; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D029968:Escherichia coli Proteins; D005353:Fibronectins; C489688:csgA protein, E coli; C077481:Crl protein, Bacteria; D003224:Congo Red