A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation.

Rosenshine, Ilan; Ruschkowski, Sharon; Stein, Murry A.; Reinscheid, Dieter J.; Mills, Scott D.

doi:10.1002/j.1460-2075.1996.tb00621.x

Cited by 252 publications

(277 citation statements)

References 33 publications

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“…We speculate that intimate attachment stabilizes the fragile EspA filaments that form putative translocation channels (Knutton et al, 1998). Another interesting implication of these results is, given that EspA and EspB are involved in activating the intimin receptor (Rosenshine et al, 1996a;Kenny et al, 1997), it appears that EspA/EspB, and intimin/Tir are involved in a positive feedback circuit between translocation and intimate attachment.…”

Section: Discussionmentioning

confidence: 69%

Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coli

Wolff

Nisan

Hanski

et al. 1998

Molecular Microbiology

197

140

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SummaryEnteropathogenic Escherichia coli (EPEC) causes diarrhoea in young children. EPEC induces the formation of actin pedestal in infected epithelial cells. A type III protein secretion system and several proteins that are secreted by this system, including EspB, are involved in inducing the formation of the actin pedestals. We have demonstrated that contact of EPEC with HeLa cells is associated with the induction of production and secretion of EspB. Shortly after infection, EPEC initiates translocation of EspB, and EspB fused to the CyaA reporter protein (EspB-CyaA), into the host cell. The translocated EspB was distributed between the membrane and the cytoplasm of the host cell. Translocation was strongly promoted by attachment of EPEC to the host cell, and both attachment factors of EPEC, intimin and the bundle-forming pili, were needed for full translocation efficiency. Translocation and secretion of EspB and EspB-CyaA were abolished in mutants deficient in components of the type III protein secretion system, including sepA and sepB mutants. EspB-CyaA was secreted but not translocated by an espB mutant. These results indicate that EspB is both translocated and required for protein translocation by EPEC.

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Section: Discussionmentioning

confidence: 69%

Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coli

Wolff

Nisan

Hanski

et al. 1998

Molecular Microbiology

197

140

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“…In addition, PKC-␣ has also been known to bind directly to the actin filaments leading to severe alterations in the cytoskeletal framework of the cell (28). Interestingly, the bacteria merely attached to HBMEC could not elicit either actin condensation or PKC-␣ localization to bacterial entry site unlike enteropathogenic E. coli, where adherence to the host cell itself triggers the activation of PKC (29).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Protein Kinase C in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

Sukumaran

Prasadarao

2002

Journal of Biological Chemistry

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Escherichia coli is one of the most important pathogens involved in the development of neonatal meningitis in many parts of the world. Traversal of E. coli across the blood-brain barrier is a crucial event in the pathogenesis of E. coli meningitis. Our previous studies have shown that outer membrane protein A (OmpA) expression is necessary in E. coli for a mechanism involving actin filaments in its passage through the endothelial cells. Focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) have also been activated in host cells during the process of invasion. In an attempt to elucidate the mechanisms leading to actin filament condensation, we have focused our attention on protein kinase C (PKC), an enzyme central to many signaling events, including actin rearrangement. In the current study, specific PKC inhibitors, bisindolmaleimide and a PKC-inhibitory peptide, inhibited E. coli invasion of human brain microvascular endothelial cells (HBMEC) by more than 75% in a dose-dependent manner, indicating a significant role played by this enzyme in the invasion process. Our results further showed that OmpA؉ E. coli induces significant activation of PKC in HBMEC as measured by the PepTag nonradioactive assay. In addition, we identified that the PKC isoform activated in E. coli invasion is a member of the conventional family of PKC, PKC-␣, which requires calcium for activation. Immunocytochemical studies have indicated that the activated PKC-␣ is associated with actin condensation beneath the bacterial entry site. Overexpression of a dominant negative mutant of PKC-␣ in HBMEC abolished the E. coli invasion without significant changes in FAK phosphorylation or PI3K activity patterns. In contrast, in HBMEC overexpressing the mutant forms of either FAK or PI3K, E. coli-induced PKC activation was significantly blocked. Furthermore, our studies showed that activation of PKC-␣ induces the translocation of myristoylated alanine-rich protein kinase C substrate, an actin cross-linking protein and a substrate for PKC-␣, from the membrane to cytosol. This is the first report of FAK-and PI3K-dependent PKC-␣ activation in bacterial invasion related to cytoskeletal reorganization.

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“…The best evidence in support of adopting such cell lines as model systems to study EPEC is the dissection of actin pedestal biogenesis, including the elucidation of the involved bacterial and host proteins. Early studies showed the process of actin pedestal formation during infection of tissue culture cells (Knutton et al 1989;Rosenshine et al 1996), which provided a solid foundation for several seminal discoveries based on the molecular mechanisms of pedestal formation during infection with A/E pathogens (reviewed in Phillips 2008 andCampellone 2010). Additional examples of the usefulness of nonpolarized cells as models for studying A/E pathogen infection are their use in studies aimed at elucidating the process of T3SS-dependent protein translocation into host cells as well as functional analyses of the injected effectors.…”

Section: In Vitro Infection Modelsmentioning

confidence: 99%

In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections

Law

Gur-Arie

Rosenshine

et al. 2013

Cold Spring Harbor Perspectives in Medicine

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Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) belong to a group of bacteria known as attaching and effacing (A/E) pathogens that cause disease by adhering to the lumenal surfaces of their host's intestinal epithelium. EPEC and EHEC are major causes of infectious diarrhea that result in significant childhood morbidity and mortality worldwide. Recent advances in in vitro and in vivo modeling of these pathogens have contributed to our knowledge of how EPEC and EHEC attach to host cells and subvert hostcell signaling pathways to promote infection and cause disease. A more detailed understanding of how these pathogenic microbes infect their hosts and how the host responds to infection could ultimately lead to new therapeutic strategies to help control these significant enteric pathogens.

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A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation.

Cited by 252 publications

References 33 publications

Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coli

Protein translocation into host epithelial cells by infecting enteropathogenic Escherichia coli

Regulation of Protein Kinase C in Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells

In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections

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