Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens

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Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens. / Arbeloa, A; Bulgin, RR; MacKenzie, G; Shaw, Robert; Pallen, Mark; Crepin, VF; Berger, CN; Frankel, G.

In: Cellular Microbiology, Vol. 10, No. 7, 01.01.2008, p. 1429-1441.

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Arbeloa, A ; Bulgin, RR ; MacKenzie, G ; Shaw, Robert ; Pallen, Mark ; Crepin, VF ; Berger, CN ; Frankel, G. / Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens. In: Cellular Microbiology. 2008 ; Vol. 10, No. 7. pp. 1429-1441.

Bibtex

@article{813082655510426bac217b986df0e86f,
title = "Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens",
abstract = "Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway.",
author = "A Arbeloa and RR Bulgin and G MacKenzie and Robert Shaw and Mark Pallen and VF Crepin and CN Berger and G Frankel",
year = "2008",
month = jan,
day = "1",
doi = "10.1111/j.1462-5822.2008.01136.x",
language = "English",
volume = "10",
pages = "1429--1441",
journal = "Cellular Microbiology",
issn = "1462-5814",
publisher = "Wiley",
number = "7",

}

RIS

TY - JOUR

T1 - Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens

AU - Arbeloa, A

AU - Bulgin, RR

AU - MacKenzie, G

AU - Shaw, Robert

AU - Pallen, Mark

AU - Crepin, VF

AU - Berger, CN

AU - Frankel, G

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway.

AB - Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway.

U2 - 10.1111/j.1462-5822.2008.01136.x

DO - 10.1111/j.1462-5822.2008.01136.x

M3 - Article

C2 - 18331467

VL - 10

SP - 1429

EP - 1441

JO - Cellular Microbiology

JF - Cellular Microbiology

SN - 1462-5814

IS - 7

ER -