Baseplate Structure of Bacteriophage Phi812 and Mechanism of Cell Wall Binding and Penetration

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00123925" target="_blank" >RIV/00216224:14740/21:00123925 - isvavai.cz</a>

Výsledek na webu

<a href="https://riccem.org/wp-content/uploads/2021/06/ijbm_11_s1_riccem-2021.pdf" target="_blank" >https://riccem.org/wp-content/uploads/2021/06/ijbm_11_s1_riccem-2021.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.21103/IJBM.11.Suppl_1.OR6" target="_blank" >10.21103/IJBM.11.Suppl_1.OR6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Baseplate Structure of Bacteriophage Phi812 and Mechanism of Cell Wall Binding and Penetration

Popis výsledku v původním jazyce

Antibiotic-resistant strains of Staphylococcus aureus cause human infections that are difficult to treat and can lead to death. Bacteriophage (phage) phi812K1/420 from the family Myoviridae infects 95% of clinical isolates of S. aureus and therefore is a promising candidate for a phage therapy agent. As the native phage particle approaches its host cell, phage receptor-binding proteins make a contact with the host cell wall. This interaction triggers a cascade of structural changes in the baseplate resulting in phage tail contraction and genome ejection. Mechanistic description of the baseplate re-organization, however, remains unknown. Methods: Using cryo-electron microscopy (cryo-EM), we studied the baseplate of the phage phi812K1/420. Also, selected proteins involved in the host cell wall binding and penetration were produced in recombinant form and their structures were solved using X-ray crystallography and cryo-EM single-particle reconstruction. Results: We reconstructed the phage baseplate in native and contracted states. The reconstruction of the native baseplate reaches resolution of 4 Å, which enables us to discern individual protein structures. Solved protein structures will be fitted into reconstruction of the contracted baseplate. Conclusion: Our results provide first structural characterization of contractile phage infecting a Gram-positive bacterium. Comparison of the two distinct baseplate states will allow us to describe molecular mechanism of initial stage of phage infection in detail.

Název v anglickém jazyce

Baseplate Structure of Bacteriophage Phi812 and Mechanism of Cell Wall Binding and Penetration

Popis výsledku anglicky

Antibiotic-resistant strains of Staphylococcus aureus cause human infections that are difficult to treat and can lead to death. Bacteriophage (phage) phi812K1/420 from the family Myoviridae infects 95% of clinical isolates of S. aureus and therefore is a promising candidate for a phage therapy agent. As the native phage particle approaches its host cell, phage receptor-binding proteins make a contact with the host cell wall. This interaction triggers a cascade of structural changes in the baseplate resulting in phage tail contraction and genome ejection. Mechanistic description of the baseplate re-organization, however, remains unknown. Methods: Using cryo-electron microscopy (cryo-EM), we studied the baseplate of the phage phi812K1/420. Also, selected proteins involved in the host cell wall binding and penetration were produced in recombinant form and their structures were solved using X-ray crystallography and cryo-EM single-particle reconstruction. Results: We reconstructed the phage baseplate in native and contracted states. The reconstruction of the native baseplate reaches resolution of 4 Å, which enables us to discern individual protein structures. Solved protein structures will be fitted into reconstruction of the contracted baseplate. Conclusion: Our results provide first structural characterization of contractile phage infecting a Gram-positive bacterium. Comparison of the two distinct baseplate states will allow us to describe molecular mechanism of initial stage of phage infection in detail.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LL1906" target="_blank" >LL1906: Replikace fágů v bakteriálním biofilmu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů