Details

Autor(en) / Beteiligte

• Latka, Agnieszka
• Lemire, Sebastien
• Grimon, Dennis
• Dams, Dorien
• Maciejewska, Barbara
• Lu, Timothy
• Drulis-Kawa, Zuzanna
• Briers, Yves
• Goldman, Gustavo H
• Goldman, Gustavo H.

Titel

Engineering the Modular Receptor-Binding Proteins of Klebsiella Phages Switches Their Capsule Serotype Specificity

Ist Teil von

• mBio, 2021-05, Vol.12 (3)

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The high specificity of bacteriophages is driven by their receptor-binding proteins (RBPs). Many bacteriophages target the capsular exopolysaccharide as the receptor and encode RBPs with depolymerase activity. The modular structure of these RBPs with an N-terminal structural module to attach the RBP to the phage tail, and a C-terminal specificity module for exopolysaccharide degradation, supports horizontal transfer as a major evolutionary driver for phage RBPs. We mimicked this natural evolutionary process by the construction of modular RBP chimeras, exchanging N-terminal structural modules and C-terminal specificity modules. All chimeras strictly follow the capsular serotype specificity of the C-terminal module. Transplanting chimeras with a K11 N-terminal structural RBP module in a phage K11 scaffold results in a capsular serotype switch and corresponding host range modification of the synthetic phages, demonstrating that horizontal transfer of C-terminal specificity modules offers phages an evolutionary highway for rapid adaptation to new capsular serotypes. The antimicrobial resistance crisis has rekindled interest in bacteriophage therapy. Phages have been studied over a century as therapeutics to treat bacterial infections, but one of the biggest challenges for the use of phages in therapeutic interventions remains their high specificity. In particular, many phages have a narrow spectrum constrained by the high diversity of exopolysaccharide capsules that shield access to the cells. In this work, we have elaborated how phages deal with this high diversity by exchanging building blocks of their receptor-binding proteins.