Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system.
The cell envelope of Gram-negative bacteria is a complex macromolecular structure, performing essential functions such as transport, respiration and protection. Moreover, it is the first line of contact between bacteria and their surroundings. Thus, maintenance of the cell envelope homeostasis is es...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Published: |
AUC Knowledge Fountain
2019
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613406715969536 |
|---|---|
| access_status_str | Open Access |
| author | Hussein, Nahla A. |
| author_browse | Hussein, Nahla A. |
| author_facet | Hussein, Nahla A. |
| author_sort | Hussein, Nahla A. |
| collection | Thesis |
| dc_rights_str_mv | The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. |
| description | The cell envelope of Gram-negative bacteria is a complex macromolecular structure, performing essential functions such as transport, respiration and protection. Moreover, it is the first line of contact between bacteria and their surroundings. Thus, maintenance of the cell envelope homeostasis is essential for bacterial survival and adaptation. In enterobacteria, the Rcs system (Regulator of capsule synthesis) monitors envelope integrity and induces a stress response when damages occur in the outer membrane or in the peptidoglycan layer. Built around a two-component system, Rcs controls gene expression via a cascade of phosphoryl transfer reactions. Being particularly complex, Rcs also involves the outer membrane lipoprotein RcsF and the inner membrane essential protein IgaA (Intracellular growth attenuator). RcsF is the stress sensor of the Rcs system while IgaA is the negative regulator, maintaining a minimal activation of the Rcs system in the absence of specific cues. Here, we establish the stress-dependent formation of a complex between RcsF and the periplasmic domain of IgaA as the molecular signal triggering Rcs, in the presence of cell-envelope targeting antibiotics. Moreover, molecular dissection of IgaA reveals that its negative regulatory role on Rcs is mostly carried by its first N-terminal cytoplasmic domain. Our analysis revealed also a contribution of IgaA transmembrane domains in its negative regulatory function. Altogether, our results support a model in which IgaA regulates Rcs activation by playing a direct role in the transfer of signals from the cell envelope to the cytoplasm. This remarkable feature further distinguishes Rcs from other envelope stress response systems and pave the way for the understanding of the molecular mechanism of the Rcs system. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-1008 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:38.861Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-1008 Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. Hussein, Nahla A. The cell envelope of Gram-negative bacteria is a complex macromolecular structure, performing essential functions such as transport, respiration and protection. Moreover, it is the first line of contact between bacteria and their surroundings. Thus, maintenance of the cell envelope homeostasis is essential for bacterial survival and adaptation. In enterobacteria, the Rcs system (Regulator of capsule synthesis) monitors envelope integrity and induces a stress response when damages occur in the outer membrane or in the peptidoglycan layer. Built around a two-component system, Rcs controls gene expression via a cascade of phosphoryl transfer reactions. Being particularly complex, Rcs also involves the outer membrane lipoprotein RcsF and the inner membrane essential protein IgaA (Intracellular growth attenuator). RcsF is the stress sensor of the Rcs system while IgaA is the negative regulator, maintaining a minimal activation of the Rcs system in the absence of specific cues. Here, we establish the stress-dependent formation of a complex between RcsF and the periplasmic domain of IgaA as the molecular signal triggering Rcs, in the presence of cell-envelope targeting antibiotics. Moreover, molecular dissection of IgaA reveals that its negative regulatory role on Rcs is mostly carried by its first N-terminal cytoplasmic domain. Our analysis revealed also a contribution of IgaA transmembrane domains in its negative regulatory function. Altogether, our results support a model in which IgaA regulates Rcs activation by playing a direct role in the transfer of signals from the cell envelope to the cytoplasm. This remarkable feature further distinguishes Rcs from other envelope stress response systems and pave the way for the understanding of the molecular mechanism of the Rcs system. 2019-02-01T08:00:00Z dissertation text/html https://fount.aucegypt.edu/etds/9 https://fount.aucegypt.edu/context/etds/article/1008/type/native/viewcontent/Nahla_20A_20Hussein_20Aly_PhD_20thesis.pdf_sequence_1 The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain IgaA Rcs system E.coli envelope stress NA |
| spellingShingle | IgaA Rcs system E.coli envelope stress NA Hussein, Nahla A. Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title | Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title_full | Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title_fullStr | Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title_full_unstemmed | Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title_short | Molecular and Functional dissection of IgaA, the negative regulator of the E.coli Rcs system. |
| title_sort | molecular and functional dissection of igaa the negative regulator of the e coli rcs system |
| topic | IgaA Rcs system E.coli envelope stress NA |
| url | https://fount.aucegypt.edu/etds/9 https://fount.aucegypt.edu/context/etds/article/1008/type/native/viewcontent/Nahla_20A_20Hussein_20Aly_PhD_20thesis.pdf_sequence_1 |
| work_keys_str_mv | AT husseinnahlaa molecularandfunctionaldissectionofigaathenegativeregulatoroftheecolircssystem |