Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule.
Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) strains represent a major global health problem. Their virulence is mediated by the concerted activity of an array of virulence factors including toxins, a type III protein secretion system (TTSS), pili, and others. We previously showed that EPEC O127 forms a group 4 capsule (G4C), and in this report we show that EHEC O157 also produces a G4C, whose assembly is dependent on the etp, etk, and wzy genes. We further show that at early time points postinfection, these G4Cs appear to mask surface structures including intimin and the TTSS. This masking inhibited the attachment of EPEC and EHEC to tissue-cultured epithelial cells, diminished their capacity to induce the formation of actin pedestals, and attenuated TTSS-mediated protein translocation into host cells. Importantly, we found that Ler, a positive regulator of intimin and TTSS genes, represses the expression of the capsule-related genes, including etp and etk. Thus, the expression of TTSS and G4C is conversely regulated and capsule production is diminished upon TTSS expression. Indeed, at later time points postinfection, the diminishing capsule no longer interferes with the activities of intimin and the TTSS. Notably, by using the rabbit infant model, we found that the EHEC G4C is required for efficient colonization of the rabbit large intestine. Taken together, our results suggest that temporal expression of the capsule, which is coordinated with that of the TTSS, is required for optimal EHEC colonization of the host intestine.
Shifrin
Yulia
Y
Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
Peleg
Adi
A
Ilan
Ophir
O
Nadler
Chen
C
Kobi
Simi
S
Baruch
Kobi
K
Yerushalmi
Gal
G
Berdichevsky
Tatiana
T
Altuvia
Shoshy
S
Elgrably-Weiss
Maya
M
Abe
Cecilia
C
Knutton
Stuart
S
Sasakawa
Chihiro
C
Ritchie
Jennifer M
JM
Waldor
Matthew K
MK
Rosenshine
Ilan
I
D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism / Q000472:pathogenicity* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000382:microbiology; D004912:Erythrocytes / Q000382:microbiology; D004927:Escherichia coli Infections; D019453:Escherichia coli O157 / Q000378:metabolism / Q000472:pathogenicity* / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007420:Intestine, Large / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D016254:Mutagenesis, Insertional; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015534:Trans-Activators / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism*
D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; C120614:Etk protein, E coli; C510011:EtpA protein, E coli; C465556:Ler protein, E coli; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C073819:eaeA protein, E coli; D016695:Glycosyltransferases; C513753:Wzy polymerase, E coli; D011505:Protein-Tyrosine Kinases