The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities
IntroductionEnteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen and one of the major causes of gastrointestinal illness in developing countries. EPEC, similar to many other Gram-negative bacterial pathogens, possesses essential virulence machinery called the type III secretion syste...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103552/full |
| _version_ | 1811164243967344640 |
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| author | Dor Braverman Jenia Gershberg Neta Sal-Man |
| author_facet | Dor Braverman Jenia Gershberg Neta Sal-Man |
| author_sort | Dor Braverman |
| collection | DOAJ |
| description | IntroductionEnteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen and one of the major causes of gastrointestinal illness in developing countries. EPEC, similar to many other Gram-negative bacterial pathogens, possesses essential virulence machinery called the type III secretion system (T3SS) that enables the injection of effector proteins from the bacteria into the host cytoplasm. Of these, the translocated intimin receptor (Tir) is the first effector to be injected, and its activity is essential for the formation of attaching and effacing lesions, the hallmark of EPEC colonization. Tir belongs to a unique group of transmembrane domain (TMD)-containing secreted proteins, which have two conflicting destination indications, one for bacterial membrane integration and another for protein secretion. In this study, we examined whether TMDs participate in the secretion, translocation, and function of Tir in host cells.MethodsWe created Tir TMD variants with the original or alternative TMD sequence.ResultsWe found that the C-terminal TMD of Tir (TMD2) is critical for the ability of Tir to escape integration into the bacterial membrane. However, the TMD sequence was not by itself sufficient and its effect was context-dependent. Moreover, the N-terminal TMD of Tir (TMD1) was important for the postsecretion function of Tir at the host cell.DiscussionTaken together, our study further supports the hypothesis that the TMD sequences of translocated proteins encode information crucial for protein secretion and their postsecretion function. |
| first_indexed | 2024-04-10T15:19:24Z |
| format | Article |
| id | doaj.art-671de9375f37402387eb37348df4df61 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-10T15:19:24Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-671de9375f37402387eb37348df4df612023-02-14T16:51:46ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-02-011310.3389/fcimb.2023.11035521103552The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activitiesDor BravermanJenia GershbergNeta Sal-ManIntroductionEnteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen and one of the major causes of gastrointestinal illness in developing countries. EPEC, similar to many other Gram-negative bacterial pathogens, possesses essential virulence machinery called the type III secretion system (T3SS) that enables the injection of effector proteins from the bacteria into the host cytoplasm. Of these, the translocated intimin receptor (Tir) is the first effector to be injected, and its activity is essential for the formation of attaching and effacing lesions, the hallmark of EPEC colonization. Tir belongs to a unique group of transmembrane domain (TMD)-containing secreted proteins, which have two conflicting destination indications, one for bacterial membrane integration and another for protein secretion. In this study, we examined whether TMDs participate in the secretion, translocation, and function of Tir in host cells.MethodsWe created Tir TMD variants with the original or alternative TMD sequence.ResultsWe found that the C-terminal TMD of Tir (TMD2) is critical for the ability of Tir to escape integration into the bacterial membrane. However, the TMD sequence was not by itself sufficient and its effect was context-dependent. Moreover, the N-terminal TMD of Tir (TMD1) was important for the postsecretion function of Tir at the host cell.DiscussionTaken together, our study further supports the hypothesis that the TMD sequences of translocated proteins encode information crucial for protein secretion and their postsecretion function.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103552/fullbacterial virulenceEPECtransmembrane domainstype III secretion systemTir |
| spellingShingle | Dor Braverman Jenia Gershberg Neta Sal-Man The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities Frontiers in Cellular and Infection Microbiology bacterial virulence EPEC transmembrane domains type III secretion system Tir |
| title | The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities |
| title_full | The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities |
| title_fullStr | The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities |
| title_full_unstemmed | The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities |
| title_short | The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities |
| title_sort | transmembrane domains of the type iii secretion system effector tir are involved in its secretion and cellular activities |
| topic | bacterial virulence EPEC transmembrane domains type III secretion system Tir |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103552/full |
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