EspFU, a type III-translocated effector of actin assembly, fosters epithelial association and late-stage intestinal colonization by E. coli O157:H7.
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 induces filamentous actin-rich 'pedestals' on intestinal epithelial cells. Pedestal formation in vitro requires translocation of bacterial effectors into the host cell, including Tir, an EHEC receptor, and EspF(U), which increases the efficiency of actin assembly initiated by Tir. While inactivation of espF(U) does not alter colonization in two reservoir hosts, we utilized two disease models to explore the significance of EspF(U)-promoted actin pedestal formation. EHECDeltaespF(U) efficiently colonized the rabbit intestine during co-infection with wild-type EHEC, but co-infection studies on cultured cells suggested that EspF(U) produced by wild-type bacteria might have rescued the mutant. Significantly, EHECDeltaespF(U) by itself was fully capable of establishing colonization at 2 days post inoculation but unlike wild type, failed to expand in numbers in the caecum and colon by 7 days. In the gnotobiotic piglet model, an espF(U) deletion mutant appeared to generate actin pedestals with lower efficiency than wild type. Furthermore, aggregates of the mutant occupied a significantly smaller area of the intestinal epithelial surface than those of the wild type. Together, these findings suggest that, after initial EHEC colonization of the intestinal surface, EspF(U) may stabilize bacterial association with the epithelial cytoskeleton and promote expansion beyond initial sites of infection.
Ritchie
Jennifer M
JM
The Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Brady
Michael J
MJ
Riley
Kathleen N
KN
Ho
Theresa Deland
TD
Campellone
Kenneth G
KG
Herman
Ira M
IM
Donohue-Rolfe
Arthur
A
Tzipori
Saul
S
Waldor
Matthew K
MK
Leong
John M
JM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001422:Bacterial Adhesion / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D019453:Escherichia coli O157 / Q000254:growth & development* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology*; D047908:Intracellular Signaling Peptides and Proteins; D011817:Rabbits; D013552:Swine; D013997:Time Factors
D000199:Actins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins