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Tir Is Essential for the Recruitment of Tks5 to Enteropathogenic Escherichia coli Pedestals

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Abstract
Enteropathogenic
Escherichia coli
(EPEC) is a bacterial pathogen that infects the epithelial
lining of the small intestine and causes diarrhea. Upon attachment to the intestinal epithe-
lium, EPEC uses a Type III Secretion System to inject its own high affinity receptor Translo-
cated intimin receptor (Tir) into the host cell. Tir facilitates tight adhesion and recruitment of
actin-regulating proteins leading to formation of an actin pedestal beneath the infecting bac-
terium. The pedestal has several similarities with podosomes, which are basolateral actin-
rich extensions found in some migrating animal cells. Formation of podosomes is depen-
dent upon the early podosome-specific scavenger protein Tks5, which is involved in actin
recruitment. Although Tks5 is expressed in epithelial cells, and podosomes and EPEC ped-
estals share many components in their structure and mechanism of formation, the potential
role of Tks5 in EPEC infections has not been studied. The aim of this study was to deter-
mine the subcellular localization of Tks5 in epithelial cells and to investigate if Tks5 is
recruited to the EPEC pedestal. In an epithelial MDCK cell line stably expressing Tks5-
EGFP, Tks5 localized to actin bundles. Upon infection, EPEC recruited Tks5-EGFP. Tir, but
not Tir phosphorylation was essential for the recruitment. Time-lapse microscopy revealed
that Tks5-EGFP was recruited instantly upon EPEC attachment to host cells, simulta-
neously with actin and N-WASp. EPEC infection of cells expressing a
Δ
PX-Tks5 deletion
version of Tks5 showed that EPEC was able to both infect and form pedestals when the PX
domain was deleted from Tks5. Future investigations will clarify the role of Tks5 in EPEC
infection and pedestal formation.
Original languageEnglish
Article numbere0141871
JournalP L o S One
Volume10
Issue11
Pages (from-to)1-16
Number of pages17
ISSN1932-6203
DOIs
Publication statusPublished - 4 Nov 2015

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