A C-terminal class I PDZ binding motif of EspI/NleA modulates the virulence of attaching and effacing Escherichia coli and Citrobacter rodentium
| Autor: | Michelle L Kelly, Roy M. Robins-Browne, Sau Fung Lee, Adrian Dale McAlister, Erin L. Garcia, Shelley Narelle Luck, Elizabeth L. Hartland, Randy A. Hall, Gad Frankel |
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| Rok vydání: | 2007 |
| Předmět: |
Virulence Factors
Immunology PDZ domain Golgi Apparatus PDZ Domains Poison control Virulence Biology Microbiology Enteropathogenic Escherichia coli Mice Bacterial Proteins Intestinal mucosa Sequence Analysis Protein Two-Hybrid System Techniques Virology Protein Interaction Mapping Citrobacter rodentium Animals Humans Secretion Peptide sequence Gene Library Escherichia coli Proteins Cell biology Mice Inbred C57BL Protein Transport HeLa Cells Locus of enterocyte effacement |
| Zdroj: | Cellular Microbiology. :071103031556003 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2007.01065.x |
| Popis: | Enteropathogenic Escherichia coli induces characteristic attaching-effacing (A/E) lesions on the intestinal mucosa during infection. The locus of enterocyte effacement is essential for A/E lesion formation and encodes a type III secretion system that translocates multiple effector proteins into the host cell. Following translocation, EspI/NleA localizes to the Golgi. Using the yeast two-hybrid system (Y2HS) and PSD-95/Disk-large/ZO-1 (PDZ)-domain protein array overlays, we identified 15 putative host-interacting partners of EspI. All but two of the target proteins contained PDZ domains. Examination of the EspI amino acid sequence revealed a C-terminal consensus class I PDZ binding motif. Deletion of the last 7 amino acids of EspI to generate EspI(DeltaC7) abrogated the Y2HS interaction between EspI and 5 of the 6 putative host cell target proteins tested. Deletion of the EspI PDZ binding motif also resulted in delayed trafficking of EspI to the Golgi. Using a mouse model of infection, we showed that Citrobacter rodentium expressing truncated EspI(DeltaC7) was attenuated when in competition with C. rodentium expressing full-length EspI. Overall, these results suggested that EspI may modulate the virulence of A/E pathogens by binding host PDZ-domain proteins. |
| Databáze: | OpenAIRE |
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