Enteropathogenic Escherichia coli O125:H6 triggers attaching and effacing lesions on human intestinal biopsy specimens independently of Nck and TccP/TccP2.
Typical enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) employ either Nck, TccP/TccP2, or Nck and TccP/TccP2 pathways to activate the neuronal Wiskott-Aldrich syndrome protein (N-WASP) and to trigger actin polymerization in cultured cells. This phenotype is used as a marker for the pathogenic potential of EPEC and EHEC strains. In this paper we report that EPEC O125:H6, which represents a large category of strains, lacks the ability to utilize either Nck or TccP/TccP2 and hence triggers actin polymerization in vitro only inefficiently. However, we show that infection of human intestinal biopsies with EPEC O125:H6 results in formation of typical attaching and effacing lesions. Expression of TccP in EPEC O125:H6, which harbors an EHEC O157-like Tir, resulted in efficient actin polymerization in vitro and enhanced colonization of human intestinal in vitro organ cultures with detectable N-WASP and electron-dense material at the site of bacterial adhesion. These results show the existence of a natural category of EPEC that colonizes the gut mucosa using Nck- and TccP-independent mechanisms. Importantly, the results highlight yet again the fact that conclusions made on the basis of in vitro cell culture models cannot be extrapolated wholesale to infection of mucosal surfaces and that the ability to induce actin polymerization on cultured cells should not be used as a definitive marker for EPEC and EHEC virulence.
Bai
Li
L
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Diseases Control and Prevention, China CDC, Beijing, China.
Schüller
Stephanie
S
Whale
Andrew
A
Mousnier
Aurelie
A
Marches
Olivier
O
Wang
Lei
L
Ooka
Tadasuke
T
Heuschkel
Robert
R
Torrente
Franco
F
Kaper
James B
JB
Gomes
Tânia A T
TA
Xu
Jianguo
J
Phillips
Alan D
AD
Frankel
Gad
G
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001422:Bacterial Adhesion; D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism*; D054308:Enteropathogenic Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007422:Intestines / Q000382:microbiology / Q000473:pathology*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C485544:NCK2 protein, human; C078332:Nck protein; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; C526042:TccP2 protein, E coli; C109287:Tir protein, E coli; C505370:tccP protein, E coli