EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation
ABSTRACT Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. Howe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2012-11-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00317-12 |
| _version_ | 1818398848702218240 |
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| author | Cedric N. Berger Valerie F. Crepin Kobi Baruch Aurelie Mousnier Ilan Rosenshine Gad Frankel |
| author_facet | Cedric N. Berger Valerie F. Crepin Kobi Baruch Aurelie Mousnier Ilan Rosenshine Gad Frankel |
| author_sort | Cedric N. Berger |
| collection | DOAJ |
| description | ABSTRACT Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal “translocation stop” activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation. IMPORTANCE Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important diarrheal pathogens responsible for significant morbidity and mortality in developing countries and the developed world, respectively. The virulence strategy of EPEC and EHEC revolves around a conserved type III secretion system (T3SS), which translocates bacterial proteins known as effectors directly into host cells. Previous studies have shown that when cells are infected in two waves with EPEC, the first wave inhibits effector translocation by the second wave in a T3SS-dependent manner, although the factor involved was not known. Importantly, we identified EspZ as the effector responsible for blocking protein translocation following a secondary EPEC infection. Interestingly, we found that while EspZ of EHEC can block protein translocation from both EPEC and EHEC strains, EPEC EspZ cannot block translocation from EHEC. These studies show that EPEC and EHEC employ a novel infection strategy to regulate T3SS translocation. |
| first_indexed | 2024-12-14T07:11:18Z |
| format | Article |
| id | doaj.art-bb00251f42bf4da3a34ef5612c0ef42c |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T07:11:18Z |
| publishDate | 2012-11-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-bb00251f42bf4da3a34ef5612c0ef42c2022-12-21T23:11:49ZengAmerican Society for MicrobiologymBio2150-75112012-11-013510.1128/mBio.00317-12EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein TranslocationCedric N. Berger0Valerie F. Crepin1Kobi Baruch2Aurelie Mousnier3Ilan Rosenshine4Gad Frankel5Centre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom,Centre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom,Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelCentre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom,Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, IsraelCentre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom,ABSTRACT Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal “translocation stop” activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation. IMPORTANCE Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important diarrheal pathogens responsible for significant morbidity and mortality in developing countries and the developed world, respectively. The virulence strategy of EPEC and EHEC revolves around a conserved type III secretion system (T3SS), which translocates bacterial proteins known as effectors directly into host cells. Previous studies have shown that when cells are infected in two waves with EPEC, the first wave inhibits effector translocation by the second wave in a T3SS-dependent manner, although the factor involved was not known. Importantly, we identified EspZ as the effector responsible for blocking protein translocation following a secondary EPEC infection. Interestingly, we found that while EspZ of EHEC can block protein translocation from both EPEC and EHEC strains, EPEC EspZ cannot block translocation from EHEC. These studies show that EPEC and EHEC employ a novel infection strategy to regulate T3SS translocation.https://journals.asm.org/doi/10.1128/mBio.00317-12 |
| spellingShingle | Cedric N. Berger Valerie F. Crepin Kobi Baruch Aurelie Mousnier Ilan Rosenshine Gad Frankel EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation mBio |
| title | EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation |
| title_full | EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation |
| title_fullStr | EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation |
| title_full_unstemmed | EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation |
| title_short | EspZ of Enteropathogenic and Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content> Regulates Type III Secretion System Protein Translocation |
| title_sort | espz of enteropathogenic and enterohemorrhagic named content content type genus species escherichia coli named content regulates type iii secretion system protein translocation |
| url | https://journals.asm.org/doi/10.1128/mBio.00317-12 |
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