Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition.
Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition mediated by CdiA effector proteins. CdiA is presented on the inhibitor cell surface and delivers its toxic C-terminal region (CdiA-CT) into neighboring bacteria upon contact. Inhibitor cells also produce Cd...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-11-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011494 |
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| author | Tiffany M Halvorsen Kaitlin A Schroeder Allison M Jones Disa Hammarlöf David A Low Sanna Koskiniemi Christopher S Hayes |
| author_facet | Tiffany M Halvorsen Kaitlin A Schroeder Allison M Jones Disa Hammarlöf David A Low Sanna Koskiniemi Christopher S Hayes |
| author_sort | Tiffany M Halvorsen |
| collection | DOAJ |
| description | Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition mediated by CdiA effector proteins. CdiA is presented on the inhibitor cell surface and delivers its toxic C-terminal region (CdiA-CT) into neighboring bacteria upon contact. Inhibitor cells also produce CdiI immunity proteins, which neutralize CdiA-CT toxins to prevent auto-inhibition. Here, we describe a diverse group of CDI ionophore toxins that dissipate the transmembrane potential in target bacteria. These CdiA-CT toxins are composed of two distinct domains based on AlphaFold2 modeling. The C-terminal ionophore domains are all predicted to form five-helix bundles capable of spanning the cell membrane. The N-terminal "entry" domains are variable in structure and appear to hijack different integral membrane proteins to promote toxin assembly into the lipid bilayer. The CDI ionophores deployed by E. coli isolates partition into six major groups based on their entry domain structures. Comparative sequence analyses led to the identification of receptor proteins for ionophore toxins from groups 1 & 3 (AcrB), group 2 (SecY) and groups 4 (YciB). Using forward genetic approaches, we identify novel receptors for the group 5 and 6 ionophores. Group 5 exploits homologous putrescine import proteins encoded by puuP and plaP, and group 6 toxins recognize di/tripeptide transporters encoded by paralogous dtpA and dtpB genes. Finally, we find that the ionophore domains exhibit significant intra-group sequence variation, particularly at positions that are predicted to interact with CdiI. Accordingly, the corresponding immunity proteins are also highly polymorphic, typically sharing only ~30% sequence identity with members of the same group. Competition experiments confirm that the immunity proteins are specific for their cognate ionophores and provide no protection against other toxins from the same group. The specificity of this protein interaction network provides a mechanism for self/nonself discrimination between E. coli isolates. |
| format | Article |
| id | doaj-art-ee7413864fbf4ac6839977ed278c5afd |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-ee7413864fbf4ac6839977ed278c5afd2025-02-07T05:30:35ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042024-11-012011e101149410.1371/journal.pgen.1011494Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition.Tiffany M HalvorsenKaitlin A SchroederAllison M JonesDisa HammarlöfDavid A LowSanna KoskiniemiChristopher S HayesContact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition mediated by CdiA effector proteins. CdiA is presented on the inhibitor cell surface and delivers its toxic C-terminal region (CdiA-CT) into neighboring bacteria upon contact. Inhibitor cells also produce CdiI immunity proteins, which neutralize CdiA-CT toxins to prevent auto-inhibition. Here, we describe a diverse group of CDI ionophore toxins that dissipate the transmembrane potential in target bacteria. These CdiA-CT toxins are composed of two distinct domains based on AlphaFold2 modeling. The C-terminal ionophore domains are all predicted to form five-helix bundles capable of spanning the cell membrane. The N-terminal "entry" domains are variable in structure and appear to hijack different integral membrane proteins to promote toxin assembly into the lipid bilayer. The CDI ionophores deployed by E. coli isolates partition into six major groups based on their entry domain structures. Comparative sequence analyses led to the identification of receptor proteins for ionophore toxins from groups 1 & 3 (AcrB), group 2 (SecY) and groups 4 (YciB). Using forward genetic approaches, we identify novel receptors for the group 5 and 6 ionophores. Group 5 exploits homologous putrescine import proteins encoded by puuP and plaP, and group 6 toxins recognize di/tripeptide transporters encoded by paralogous dtpA and dtpB genes. Finally, we find that the ionophore domains exhibit significant intra-group sequence variation, particularly at positions that are predicted to interact with CdiI. Accordingly, the corresponding immunity proteins are also highly polymorphic, typically sharing only ~30% sequence identity with members of the same group. Competition experiments confirm that the immunity proteins are specific for their cognate ionophores and provide no protection against other toxins from the same group. The specificity of this protein interaction network provides a mechanism for self/nonself discrimination between E. coli isolates.https://doi.org/10.1371/journal.pgen.1011494 |
| spellingShingle | Tiffany M Halvorsen Kaitlin A Schroeder Allison M Jones Disa Hammarlöf David A Low Sanna Koskiniemi Christopher S Hayes Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. PLoS Genetics |
| title | Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. |
| title_full | Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. |
| title_fullStr | Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. |
| title_full_unstemmed | Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. |
| title_short | Contact-dependent growth inhibition (CDI) systems deploy a large family of polymorphic ionophoric toxins for inter-bacterial competition. |
| title_sort | contact dependent growth inhibition cdi systems deploy a large family of polymorphic ionophoric toxins for inter bacterial competition |
| url | https://doi.org/10.1371/journal.pgen.1011494 |
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