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@proceedings{2346965,
author = {Bíňovský, Ján and Šiborová, Marta and Nováček, Jiří and Škubník, Karel and Botka, Tibor and Benešík, Martin and Pantůček, Roman and VAN RAAIJ, MARK and Plevka, Pavel},
booktitle = {2nd Meeting of the National Institute of Virology and Bacteriology (NIVB) in Kutná Hora, Czech Chemical Society Symposium Series vol. 21, no. 5, s. 177-256},
keywords = {S. aureus; phage; phi812; structure; cryo-EM},
language = {eng},
title = {Conformational changes in baseplate required for genome delivery of S. aureus phage phi812},
url = {http://www.ccsss.cz/index.php/ccsss/issue/view/41},
year = {2023}
}
TY - CONF
ID - 2346965
AU - Bíňovský, Ján - Šiborová, Marta - Nováček, Jiří - Škubník, Karel - Botka, Tibor - Benešík, Martin - Pantůček, Roman - VAN RAAIJ, MARK - Plevka, Pavel
PY - 2023
TI - Conformational changes in baseplate required for genome delivery of S. aureus phage phi812
KW - S. aureus
KW - phage
KW - phi812
KW - structure
KW - cryo-EM
UR - http://www.ccsss.cz/index.php/ccsss/issue/view/41
N2 - 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.
ER -
BÍŇOVSKÝ, Ján, Marta ŠIBOROVÁ, Jiří NOVÁČEK, Karel ŠKUBNÍK, Tibor BOTKA, Martin BENEŠÍK, Roman PANTŮČEK, MARK VAN RAAIJ a Pavel PLEVKA. Conformational changes in baseplate required for genome delivery of S. aureus phage phi812. In \textit{2nd Meeting of the National Institute of Virology and Bacteriology (NIVB) in Kutná Hora, Czech Chemical Society Symposium Series vol. 21, no. 5, s. 177-256}. 2023. ISSN~2336-7210.
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