Open AccessA C‐terminal class I PDZ binding motif of EspI/NleA modulates the virulence of attaching and effacing Escherichia coli and Citrobacter rodentium
Author(s) -
Lee Sau Fung,
Kelly Michelle,
McAlister Adrian,
Luck Shelley N.,
Garcia Erin L.,
Hall Randy A.,
RobinsBrowne Roy M.,
Frankel Gad,
Hartland Elizabeth L.
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01065.x
Subject(s) - pdz domain , biology , citrobacter rodentium , virulence , golgi apparatus , effector , escherichia coli , citrobacter , microbiology and biotechnology , gene , genetics , enterobacteriaceae , endoplasmic reticulum
Summary 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 ΔC7 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 ΔC7 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.