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>

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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Bibliographic Details
Main Authors: Dorien Dams, Célia Pas, Agnieszka Latka, Zuzanna Drulis-Kawa, Lars Fieseler, Yves Briers
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
Subjects:
tailocin
phage tail-like bacteriocin
R2 pyocin
<i>Klebsiella pneumoniae</i>
<i>Escherichia coli</i>
receptor-binding protein
Online Access:https://www.mdpi.com/2079-6382/14/1/104
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Summary:<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.
ISSN:2079-6382

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