A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>
<b>Background:</b> Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP e...
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2025-01-01
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| author | Dorien Dams Célia Pas Agnieszka Latka Zuzanna Drulis-Kawa Lars Fieseler Yves Briers |
| author_facet | Dorien Dams Célia Pas Agnieszka Latka Zuzanna Drulis-Kawa Lars Fieseler Yves Briers |
| author_sort | Dorien Dams |
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| description | <b>Background:</b> Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the target range of a selected R2 tailocin from <i>Pseudomonas aeruginosa</i>, the process is labor-intensive, limiting broader application. <b>Methods:</b> We introduce a VersaTile-driven R2 tailocin engineering and screening platform to scale up RBP grafting. <b>Results:</b> This platform achieved three key milestones: (I) engineering R2 tailocins specific to <i>Escherichia coli</i> serogroups O26, O103, O104, O111, O145, O146, and O157; (II) reprogramming R2 tailocins to target, for the first time, the capsule and a new species, specifically the capsular serotype K1 of <i>E. coli</i> and K11 and K63 of <i>Klebsiella pneumoniae</i>; (III) creating the first bivalent tailocin with a branched RBP and cross-species activity, effective against both <i>E. coli</i> K1 and <i>K. pneumoniae</i> K11. Over 90% of engineered tailocins were effective, with clear pathways for further optimization identified. <b>Conclusions:</b> This work lays the groundwork for a scalable platform for the development of engineered tailocins, marking an important step towards making R2 tailocins a practical therapeutic tool for targeted bacterial infections. |
| format | Article |
| id | doaj-art-5c1394884cbf42d090294a8cd383c5b1 |
| institution | Kabale University |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-5c1394884cbf42d090294a8cd383c5b12025-01-24T13:19:01ZengMDPI AGAntibiotics2079-63822025-01-0114110410.3390/antibiotics14010104A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>Dorien Dams0Célia Pas1Agnieszka Latka2Zuzanna Drulis-Kawa3Lars Fieseler4Yves Briers5Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000 Gent, BelgiumDepartment of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000 Gent, BelgiumDepartment of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000 Gent, BelgiumDepartment of Pathogen Biology and Immunology, University of Wroclaw, Przybyszewskiego 63, 51-148 Wroclaw, PolandInstitute of Food and Beverage Innovation, Food Microbiology Research Group, Zurich University of Applied Sciences (ZHAW), Einsiedlerstrasse 35, 8820 Wädenswil, SwitzerlandDepartment of Biotechnology, Ghent University, Valentin Vaerwyckweg 1, 9000 Gent, Belgium<b>Background:</b> Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the target range of a selected R2 tailocin from <i>Pseudomonas aeruginosa</i>, the process is labor-intensive, limiting broader application. <b>Methods:</b> We introduce a VersaTile-driven R2 tailocin engineering and screening platform to scale up RBP grafting. <b>Results:</b> This platform achieved three key milestones: (I) engineering R2 tailocins specific to <i>Escherichia coli</i> serogroups O26, O103, O104, O111, O145, O146, and O157; (II) reprogramming R2 tailocins to target, for the first time, the capsule and a new species, specifically the capsular serotype K1 of <i>E. coli</i> and K11 and K63 of <i>Klebsiella pneumoniae</i>; (III) creating the first bivalent tailocin with a branched RBP and cross-species activity, effective against both <i>E. coli</i> K1 and <i>K. pneumoniae</i> K11. Over 90% of engineered tailocins were effective, with clear pathways for further optimization identified. <b>Conclusions:</b> This work lays the groundwork for a scalable platform for the development of engineered tailocins, marking an important step towards making R2 tailocins a practical therapeutic tool for targeted bacterial infections.https://www.mdpi.com/2079-6382/14/1/104tailocinphage tail-like bacteriocinR2 pyocin<i>Klebsiella pneumoniae</i><i>Escherichia coli</i>receptor-binding protein |
| spellingShingle | Dorien Dams Célia Pas Agnieszka Latka Zuzanna Drulis-Kawa Lars Fieseler Yves Briers A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Antibiotics tailocin phage tail-like bacteriocin R2 pyocin <i>Klebsiella pneumoniae</i> <i>Escherichia coli</i> receptor-binding protein |
| title | A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> |
| title_full | A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> |
| title_fullStr | A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> |
| title_full_unstemmed | A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> |
| title_short | A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> |
| title_sort | versatile approach to reprogram the specificity of the r2 type tailocin towards different serotypes of i escherichia coli i and i klebsiella pneumoniae i |
| topic | tailocin phage tail-like bacteriocin R2 pyocin <i>Klebsiella pneumoniae</i> <i>Escherichia coli</i> receptor-binding protein |
| url | https://www.mdpi.com/2079-6382/14/1/104 |
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