The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL

ABSTRACT The type III secretion system (T3SS) is a multiprotein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. To ensure that effector proteins are efficiently translocated into the host cell, bacteria must be able to sense their contact with the host c...

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Autores principales: Lihi Shaulov, Jenia Gershberg, Wanyin Deng, B. Brett Finlay, Neta Sal-Man
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Publicado: American Society for Microbiology 2017
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spelling oai:doaj.org-article:5ce7acc2076042908e85b630d44fab9b2021-11-15T15:51:07ZThe Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL10.1128/mBio.01733-162150-7511https://doaj.org/article/5ce7acc2076042908e85b630d44fab9b2017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01733-16https://doaj.org/toc/2150-7511ABSTRACT The type III secretion system (T3SS) is a multiprotein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. To ensure that effector proteins are efficiently translocated into the host cell, bacteria must be able to sense their contact with the host cell. In this study, we found that EscP, which was previously shown to function as the ruler protein of the enteropathogenic Escherichia coli T3SS, is also involved in the switch from the secretion of translocator proteins to the secretion of effector proteins. In addition, we demonstrated that EscP can interact with the gatekeeper protein SepL and that the EscP-SepL complex dissociates upon a calcium concentration drop. We suggest a model in which bacterial contact with the host cell is accompanied by a drop in the calcium concentration that causes SepL-EscP complex dissociation and triggers the secretion of effector proteins. IMPORTANCE The emergence of multidrug-resistant bacterial strains, especially those of pathogenic bacteria, has serious medical and clinical implications. At the same time, the development and approval of new antibiotics have been limited for years. Recently, antivirulence drugs have received considerable attention as a novel antibiotic strategy that specifically targets bacterial virulence rather than growth, an approach that applies milder evolutionary pressure on the bacteria to develop resistance. A highly attractive target for the development of antivirulence compounds is the type III secretion system, a specialized secretory system possessed by many Gram-negative bacterial pathogens for injecting virulence factors (effectors) into host cells. In this study, we shed light on the molecular mechanism that allows bacteria to sense their contact with the host cell and to respond with the timed secretion of effector proteins. Understanding this critical step for bacterial virulence may provide a new therapeutic strategy.Lihi ShaulovJenia GershbergWanyin DengB. Brett FinlayNeta Sal-ManAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Lihi Shaulov
Jenia Gershberg
Wanyin Deng
B. Brett Finlay
Neta Sal-Man
The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
description ABSTRACT The type III secretion system (T3SS) is a multiprotein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. To ensure that effector proteins are efficiently translocated into the host cell, bacteria must be able to sense their contact with the host cell. In this study, we found that EscP, which was previously shown to function as the ruler protein of the enteropathogenic Escherichia coli T3SS, is also involved in the switch from the secretion of translocator proteins to the secretion of effector proteins. In addition, we demonstrated that EscP can interact with the gatekeeper protein SepL and that the EscP-SepL complex dissociates upon a calcium concentration drop. We suggest a model in which bacterial contact with the host cell is accompanied by a drop in the calcium concentration that causes SepL-EscP complex dissociation and triggers the secretion of effector proteins. IMPORTANCE The emergence of multidrug-resistant bacterial strains, especially those of pathogenic bacteria, has serious medical and clinical implications. At the same time, the development and approval of new antibiotics have been limited for years. Recently, antivirulence drugs have received considerable attention as a novel antibiotic strategy that specifically targets bacterial virulence rather than growth, an approach that applies milder evolutionary pressure on the bacteria to develop resistance. A highly attractive target for the development of antivirulence compounds is the type III secretion system, a specialized secretory system possessed by many Gram-negative bacterial pathogens for injecting virulence factors (effectors) into host cells. In this study, we shed light on the molecular mechanism that allows bacteria to sense their contact with the host cell and to respond with the timed secretion of effector proteins. Understanding this critical step for bacterial virulence may provide a new therapeutic strategy.
format article
author Lihi Shaulov
Jenia Gershberg
Wanyin Deng
B. Brett Finlay
Neta Sal-Man
author_facet Lihi Shaulov
Jenia Gershberg
Wanyin Deng
B. Brett Finlay
Neta Sal-Man
author_sort Lihi Shaulov
title The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
title_short The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
title_full The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
title_fullStr The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
title_full_unstemmed The Ruler Protein EscP of the Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL
title_sort ruler protein escp of the enteropathogenic <italic toggle="yes">escherichia coli</italic> type iii secretion system is involved in calcium sensing and secretion hierarchy regulation by interacting with the gatekeeper protein sepl
publisher American Society for Microbiology
publishDate 2017
url https://doaj.org/article/5ce7acc2076042908e85b630d44fab9b
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