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Signals triggered by enteropathogenic Escherichia coli in epithelial cells Foubister, Vida Joan
Abstract
Enteropathogenic Escherichia coli (EPEC) is a leading cause of infantile diarrhea in developing countries. Upon attachment to cultured epithelial cells, EPEC triggers a number of eucaryotic signals including host cell protein phosphorylation and increases in intracellular calcium. These signals function to initiate cytoskeletal rearrangement and other changes in infected cells. Intracellular and extracellular calcium was shown to be involved in bacterial attachment and entry into HeLa cells. In addition the level of inositol phosphates (IPs) increased in eucaryotic cells following EPEC addition. EPEC induced release of IPs preceded actin rearrangement beneath the attached bacterium and invasion. Noninvasive EPEC mutants and tyrosine protein kinase inhibitors were used to demonstrate that the formation of IPs depends on tyrosine phosphorylation of eucaryotic cell proteins. Inhibitors of host protein tyrosine phosphatases (02)vanadate/H₂O₂ promote uptake of EPEC into HeLa cells, supporting a role for host cell tyrosine phosphorylation in EPEC invasion. Collectively, these results highlight the essential role of host cell second messengers in EPEC infection. Several EPEC loci have been identified and found to be involved in events occurring prior to invasion, including adherence, cytoskeletal rearrangements, and the activation of host cell signals. The cfm genes are necessary for the tyrosine phosphorylation of a eucaryotic protein (Hp90). A second chromosomal locus, eaeA, encodes a 94-kDa outer membrane protein (intimin) that is essential for the establishment of intimate adherence and invasion and contributes to virulence. Recently an additional locus (eaeB), which maps approximately 5 kb downstream of the eaeA gene, was identified. Mutants carrying a deletion in the eaeB gene (UMD864) were deficient for invasion and induction of actin rearrangement, and did not attach intimately to eukaryotic cells. The AeaeB mutant was also unable to activate epithelial cell signals, including tyrosine phosphorylation of Hp90 and the release of IPs. Coinfection of HeLa cells with eaeA and eaeB mutants restored all of the phenotypes associated with attaching and effacing lesion formation. These data indicate that the EaeB protein is necessary for induction of host cell signals in infected cells, and that it has a different function than the eaeA gene product, intimin.
Item Metadata
Title |
Signals triggered by enteropathogenic Escherichia coli in epithelial cells
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1994
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Description |
Enteropathogenic Escherichia coli (EPEC) is a leading cause of infantile diarrhea in
developing countries. Upon attachment to cultured epithelial cells, EPEC triggers a
number of eucaryotic signals including host cell protein phosphorylation and increases in
intracellular calcium. These signals function to initiate cytoskeletal rearrangement and
other changes in infected cells. Intracellular and extracellular calcium was shown to be
involved in bacterial attachment and entry into HeLa cells. In addition the level of
inositol phosphates (IPs) increased in eucaryotic cells following EPEC addition. EPEC
induced release of IPs preceded actin rearrangement beneath the attached bacterium and
invasion. Noninvasive EPEC mutants and tyrosine protein kinase inhibitors were used to
demonstrate that the formation of IPs depends on tyrosine phosphorylation of eucaryotic
cell proteins. Inhibitors of host protein tyrosine phosphatases (02)vanadate/H₂O₂ promote
uptake of EPEC into HeLa cells, supporting a role for host cell tyrosine phosphorylation
in EPEC invasion. Collectively, these results highlight the essential role of host cell
second messengers in EPEC infection.
Several EPEC loci have been identified and found to be involved in events
occurring prior to invasion, including adherence, cytoskeletal rearrangements, and the
activation of host cell signals. The cfm genes are necessary for the tyrosine
phosphorylation of a eucaryotic protein (Hp90). A second chromosomal locus, eaeA,
encodes a 94-kDa outer membrane protein (intimin) that is essential for the establishment
of intimate adherence and invasion and contributes to virulence. Recently an additional
locus (eaeB), which maps approximately 5 kb downstream of the eaeA gene, was
identified. Mutants carrying a deletion in the eaeB gene (UMD864) were deficient for
invasion and induction of actin rearrangement, and did not attach intimately to eukaryotic cells. The AeaeB mutant was also unable to activate epithelial cell signals, including
tyrosine phosphorylation of Hp90 and the release of IPs. Coinfection of HeLa cells with
eaeA and eaeB mutants restored all of the phenotypes associated with attaching and
effacing lesion formation. These data indicate that the EaeB protein is necessary for
induction of host cell signals in infected cells, and that it has a different function than the
eaeA gene product, intimin.
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Extent |
2479596 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-02-24
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0087426
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1994-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.