Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function

McNamara, Barry P.; Koutsouris, Athanasia; O'Connell, Colin B.; Nougayrède, Jean-Philippe; Donnenberg, Michael S.; Hecht, Gail

doi:10.1172/jci11138

Cited by 315 publications

(337 citation statements)

References 38 publications

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“…1D). A control espF-deficient strain that is partially defective in barrier-disrupting activity, but is able to induce actin polymerization (34), did induce the recruitment, as the wild-type EPEC did (data not shown). The expression of the respective gene in the ⌬tir or ⌬eae mutant from plasmids restored the ability to recruit ZO-1 (data not shown).…”

Section: Resultsmentioning

confidence: 87%

“…Amieva and colleagues have reported that Helicobacter pylori causes a similar recruitment of ZO-1 to the bacterial attachment sites in Madin-Darby canine kidney (MDCK) cell monolayers and proposed that the recruitment is linked to a dysfunctional paracellular seal (1). Because EPEC has been reported to affect the integrity of the epithelial barrier (11,32,34,36,37,43,54), we examined if the EPEC-induced recruitment of ZO-1 is also linked with the disruption of the barrier. A polarized Caco/B7 monolayer was infected with wild-type EPEC and the mutants, and the TER across the monolayer, which is a hallmark of the integrity of the epithelial barrier, was measured.…”

Section: Resultsmentioning

confidence: 95%

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Enteropathogenic Escherichia coli , Shigella flexneri , and Listeria monocytogenes Recruit a Junctional Protein, Zonula Occludens-1, to Actin Tails and Pedestals

et al. 2007

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Enteropathogenic Escherichia coli, Shigella flexneri, and Listeria monocytogenes induce localized actin polymerization at the cytoplasmic face of the plasma membrane or within the host cytoplasm, creating unique actin-rich structures termed pedestals or actin tails. The process is known to be mediated by the actin-related protein 2 and 3 (Arp2/3) complex, which in these cases acts downstream of neural Wiskott-Aldrich syndrome protein (N-WASP) or of a listerial functional homolog of WASP family proteins. Here, we show that zonula occludens-1 (ZO-1), a protein in the tight junctions of polarized epithelial cells, is recruited to actin tails and pedestals. Immunocytochemical analysis revealed that ZO-1 was stained most in the distal part of the actin-rich structures, and the incorporation was mediated by the proline-rich region of the ZO-1 molecule. The direct clustering of membrane-targeted Nck, which is known to activate the N-WASP-Arp2/3 pathway, triggered the formation of the ZO-1-associated actin tails. The results suggest that the activation of the Arp2/3 complex downstream of N-WASP or a WASP-related molecule is a key to the formation of the particular actin-rich structures that bind with ZO-1. We propose that an analysis of the recruitment on a molecular basis will lead to an understanding of how ZO-1 recognizes a distinctive actin-rich structure under pathophysiological conditions.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 95%

Enteropathogenic Escherichia coli , Shigella flexneri , and Listeria monocytogenes Recruit a Junctional Protein, Zonula Occludens-1, to Actin Tails and Pedestals

et al. 2007

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“…An espF mutant strain exhibits normal attaching and effacing activity (26) but fails to provoke a decrease in transepithelial electrical resistance -a phenotype, found in wild-type EPEC strains, that may be related to loss of intestinal barrier function and diarrhea in vivo (in this issue, ref. 27). In addition, the espF mutant fails to induce apoptosis in host cells, another feature of the EPEC-host cell interaction (28).…”

Section: Bacterial Polymorphismsmentioning

confidence: 99%

Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Donnenberg¹,

Whittam²

2001

J. Clin. Invest.

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239

170

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“…Three additional proteins, EspA, EspB and EspD, are required for protein translocation into host cells but not for secretion . Five EPEC effectors were identified that are translocated by TTSS into the host cell: Tir (EspE), EspB, EspF, EspG and Map Deibel et al, 1998;Wolff et al, 1998;Kenny and Jepson, 2000;Crane et al, 2001;Elliott et al, 2001;McNamara et al, 2001). Map appears to interfere with the mitochondria membrane potential (Kenny and Jepson, 2000).…”

mentioning

confidence: 99%

“…Tir is involved in the formation of actin-containing protrusions, termed actin pedestals or attaching and effacing (A/E) lesions Deibel et al, 1998). EspF has been implicated in the disruption of tight junction structure and in the induction of apoptosis (Crane et al, 2001;McNamara et al, 2001). No apparent phenotype was identified in espG knock-out (Elliott et al, 2001).…”

mentioning

confidence: 99%

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

et al. 2002

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SummaryEnteropathogenic Escherichia coli (EPEC) is a human-specific pathogen that causes severe diarrhoea in young children. The disease involves intimate interaction between the pathogen and the brush border of enterocytes. During infection, EPEC uses a type III secretion system (TTSS) to inject several proteins into the infected cells, and these effector proteins modify specific processes in the host cell. We show that, upon infection, EPEC induces detachment of the infected host cells from the substratum, modification of focal adhesions (FA) in the infected cells and specific dephosphorylation of focal adhesion kinase (FAK). We also show that EPEC-induced cell detachment is dependent on FAK expression by the infected cells. Finally, we demonstrate that cell detachment, FA modification and FAK dephosphorylation are dependent on functional TTSS in the infecting EPEC. These results suggest that EPEC is using its TTSS to inject protein(s) into the infected cells, which can induce FAK dephosphorylation, as well as FAK-dependent FA modification and cell detachment. These processes are specific and probably play an important role in EPEC virulence.

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Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function

Cited by 315 publications

References 38 publications

Enteropathogenic Escherichia coli , Shigella flexneri , and Listeria monocytogenes Recruit a Junctional Protein, Zonula Occludens-1, to Actin Tails and Pedestals

Enteropathogenic Escherichia coli , Shigella flexneri , and Listeria monocytogenes Recruit a Junctional Protein, Zonula Occludens-1, to Actin Tails and Pedestals

Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

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