Enteropathogenic E. coli Effectors EspG1/G2 Disrupt Microtubules, Contribute to Tight Junction Perturbation and Inhibit Restoration Journal Article

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Authors: Glotfelty, L. G.; Zahs, A.; Hodges, K.; Shan, K.; Alto, N. M.; Hecht, G. A.
Article Title: Enteropathogenic E. coli Effectors EspG1/G2 Disrupt Microtubules, Contribute to Tight Junction Perturbation and Inhibit Restoration
Abstract: Enteropathogenic Escherichia coli (EPEC) uses a type 3 secretion system to transfer effector proteins into the host intestinal epithelial cell. Several effector molecules contribute to tight junction disruption including EspG1 and its homolog EspG2 via a mechanism thought to involve microtubule destruction. The aim of this study was to investigate the contribution of EspG-mediated microtubule disruption to TJ perturbation. We demonstrate that wild type EPEC infection disassembles microtubules and induces the progressive movement of occludin away from the membrane and into the cytosol. Deletion of espG1/G2 attenuates both of these phenotypes. In addition, EPEC infection impedes barrier recovery from calcium switch, suggesting that inhibition of TJ restoration, not merely disruption, prolongs barrier loss. TJs recover more rapidly following infection with DeltaespG1/G2 than with wild type EPEC, demonstrating that EspG1/G2 perpetuate barrier loss. Although EspG regulates ADP-ribosylation factor (ARF) and p21-activated kinase (PAK), these activities are not necessary for microtubule destruction or perturbation of TJ structure and function. These data strongly support a role for EspG1/G2 and its associated effects on microtubules in delaying the recovery of damaged tight junctions caused by EPEC infection.
Journal Title: Cellular microbiology
Volume: 16
Issue: 12
ISSN: 1462-5822; 1462-5814
Publisher: Unknown  
Date Published: 2014
Start Page: 1767
End Page: 1783
Language: ENG
DOI/URL:

10.1111/cmi.12323
Notes: LR: 20150805; CI: (c) 2014; GR: DK067887/DK/NIDDK NIH HHS/United States; GR: DK091151/DK/NIDDK NIH HHS/United States; GR: DK50694/DK/NIDDK NIH HHS/United States; GR: DK58964/DK/NIDDK NIH HHS/United States; GR: F30 DK091151/DK/NIDDK NIH HHS/United States; GR: GM100486/GM/NIGMS NIH HHS/United States; GR: I01 BX000785/BX/BLRD VA/United States; GR: P01 DK067887/DK/NIDDK NIH HHS/United States; GR: R01 DK058964/DK/NIDDK NIH HHS/United States; GR: R01 DK097043/DK/NIDDK NIH HHS/United States; GR: R01 GM100486/GM/NIGMS NIH HHS/United States; GR: R56 DK050694/DK/NIDDK NIH HHS/United States; JID: 100883691; 0 (Escherichia coli Proteins); 0 (EspG1 protein, E coli); 0 (EspG2 protein, E coli); 0 (Microtubule-Associated Proteins); 0 (Virulence Factors); NIHMS641830; OID: NLM: NIHMS641830 [Available on 12/01/15]; OID: NLM: PMC4451209 [Available on 12/01/15]; PMCR: 2015/12/01 00:00; 2013/07/28 [received]; 2014/05/20 [revised]; 2014/06/05 [accepted]; 2014/08/07 [aheadofprint]; ppublish