Conformational changes in baseplate required for genome delivery of S. aureus phage phi812

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F23%3A00132440" target="_blank" >RIV/00216224:14740/23:00132440 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.ccsss.cz/index.php/ccsss/issue/view/41" target="_blank" >http://www.ccsss.cz/index.php/ccsss/issue/view/41</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Conformational changes in baseplate required for genome delivery of S. aureus phage phi812

Popis výsledku v původním jazyce

Molecular machines such as bacteriophages with contractile tails and contractile injection systems employ a syringe-like mechanism to penetrate the host cell envelope. While most structurally characterized contractile machines aim at Gram-negative bacteria or eukaryotic cells, detailed structures of those targeting Gram-positive bacteria are lacking. Here we present a structural analysis of the baseplate and tail of contractile-tailed phage phi812, which infects Gram-positive Staphylococcus aureus. We show that instead of fibers, phi812 binds to the cell wall using six rigid baseplate arms with two types of primary receptor-binding complexes and twelve robust pyramidal complexes. Using an integrative approach, we determined the protein structures in the tail tip complex, which orchestrates the degradation of the host cell wall. We further show that the distinct tail sheath structure allows for the flexibility of the contractile tail and that interaction between the sheath and baseplate is reflected in the conformational adaptation of the baseplate-proximal sheath. Finally, comparing the pre-attachment (native) and post-attachment (contracted) states of the baseplate and tail of phi812 provides mechanistic insights into the cascade of conformational changes within the baseplate, leading to tail sheath contraction and penetration of the host cell. This study represents the first detailed structural characterization of a bacteriophage with a contractile tail infecting a Gram-positive bacterium and sheds light on the initial stages of bacteriophage infection on the molecular level. As the host-range mutants of phage phi812 exhibit exceptional efficacy in eradicating S. aureus, our findings provide a solid foundation for engineering phage particles to combat S. aureus infections in humans and pave the way for novel therapeutic applications.

Název v anglickém jazyce

Conformational changes in baseplate required for genome delivery of S. aureus phage phi812

Popis výsledku anglicky

Molecular machines such as bacteriophages with contractile tails and contractile injection systems employ a syringe-like mechanism to penetrate the host cell envelope. While most structurally characterized contractile machines aim at Gram-negative bacteria or eukaryotic cells, detailed structures of those targeting Gram-positive bacteria are lacking. Here we present a structural analysis of the baseplate and tail of contractile-tailed phage phi812, which infects Gram-positive Staphylococcus aureus. We show that instead of fibers, phi812 binds to the cell wall using six rigid baseplate arms with two types of primary receptor-binding complexes and twelve robust pyramidal complexes. Using an integrative approach, we determined the protein structures in the tail tip complex, which orchestrates the degradation of the host cell wall. We further show that the distinct tail sheath structure allows for the flexibility of the contractile tail and that interaction between the sheath and baseplate is reflected in the conformational adaptation of the baseplate-proximal sheath. Finally, comparing the pre-attachment (native) and post-attachment (contracted) states of the baseplate and tail of phi812 provides mechanistic insights into the cascade of conformational changes within the baseplate, leading to tail sheath contraction and penetration of the host cell. This study represents the first detailed structural characterization of a bacteriophage with a contractile tail infecting a Gram-positive bacterium and sheds light on the initial stages of bacteriophage infection on the molecular level. As the host-range mutants of phage phi812 exhibit exceptional efficacy in eradicating S. aureus, our findings provide a solid foundation for engineering phage particles to combat S. aureus infections in humans and pave the way for novel therapeutic applications.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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