Strain-dependent induction of epithelial cell oncosis by Campylobacter jejuni is correlated with invasion ability and is independent of cytolethal distending toxin.
Induction of host cell death is thought to play an important role in bacterial pathogenesis. Campylobacter jejuni is a prevalent cause of bacterial enteritis; however, its effects on enterocytes remain unclear. The present study indicates for the first time that C. jejuni induces oncotic, rather than apoptotic death of T84 enterocytes. C. jejuni-treated enterocytes exhibited extensive cytoplasmic vacuolation, rapid (3-6 h) loss of plasma membrane integrity ('cytotoxicity'), loss of mitochondrial transmembrane potential, and ATP depletion. Enterocytes also exhibited increased oligonucleosomal DNA fragmentation, a feature characteristic of apoptosis. However, consistent with a non-apoptotic process, DNA fragmentation and cytotoxicity were not caspase dependent. During apoptosis, caspases mediate cleavage of poly(ADP-ribose) polymerase; however, cleavage was not observed in C. jejuni-treated monolayers. Cytotoxicity, ATP depletion and DNA fragmentation were not prevented by the deletion of the cytolethal distending toxin (CDT) gene, indicating that C. jejuni causes enterocyte oncosis via a mechanism that is CDT independent. The ability to cause oncosis was significantly decreased in a FlaAFlaB mutant (CDT(+)) that was defective in the ability to adhere and invade enterocytes. Analysis of clinical isolates revealed that oncosis was strain dependent and correlated with increased invasive ability. These observations offer new insights into the pathogenesis of C. jejuni infection.
Kalischuk
Lisa D
LD
Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB T1J 4B1, Canada.|Department of Biological Sciences, Inflammation Research Network, University of Calgary, Bio 336, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
Inglis
G Douglas
GD
Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB T1J 4B1, Canada.
Buret
Andre G
AG
Department of Biological Sciences, Inflammation Research Network, University of Calgary, Bio 336, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D016123:Campylobacter jejuni / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016923:Cell Death; D002460:Cell Line; D020895:Enterocytes / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009154:Mutation; D013045:Species Specificity
D001427:Bacterial Toxins; C067044:cytolethal distending toxin