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@article{2254857,
author = {Kuntová, Lucie and Mašlaňová, Ivana and Obořilová, Radka and Šimečková, Hana and Finstrlová, Adéla and Bárdy, Pavol and Šiborová, Marta and Troianovska, Liudmyla and Botka, Tibor and Gintar, Petr and Šedo, Ondrej and Farka, Zdeněk and Doškař, Jiří and Pantůček, Roman},
article_location = {Washington, DC, USA},
article_number = {2},
doi = {http://dx.doi.org/10.1128/mbio.02490-22},
keywords = {Staphylococcus aureus; lysogeny; phage resistance; abortive infection; Kayvirus; cell death; phage therapy; bacteriophage evolution; bacteriophage therapy; bacteriophages},
language = {eng},
issn = {2150-7511},
journal = {mBio},
title = {Staphylococcus aureus Prophage-Encoded Protein Causes Abortive Infection and Provides Population Immunity against Kayviruses},
url = {https://journals.asm.org/doi/10.1128/mbio.02490-22},
volume = {14},
year = {2023}
}
TY - JOUR
ID - 2254857
AU - Kuntová, Lucie - Mašlaňová, Ivana - Obořilová, Radka - Šimečková, Hana - Finstrlová, Adéla - Bárdy, Pavol - Šiborová, Marta - Troianovska, Liudmyla - Botka, Tibor - Gintar, Petr - Šedo, Ondrej - Farka, Zdeněk - Doškař, Jiří - Pantůček, Roman
PY - 2023
TI - Staphylococcus aureus Prophage-Encoded Protein Causes Abortive Infection and Provides Population Immunity against Kayviruses
JF - mBio
VL - 14
IS - 2
SP - 1-15
EP - 1-15
PB - American Society for Microbiology
SN - 21507511
KW - Staphylococcus aureus
KW - lysogeny
KW - phage resistance
KW - abortive infection
KW - Kayvirus
KW - cell death
KW - phage therapy
KW - bacteriophage evolution
KW - bacteriophage therapy
KW - bacteriophages
UR - https://journals.asm.org/doi/10.1128/mbio.02490-22
N2 - Both temperate and obligately lytic phages have crucial roles in the biology of staphylococci. While superinfection exclusion among closely related temperate phages is a well-characterized phenomenon, the interactions between temperate and lytic phages in staphylococci are not understood. Here, we present a resistance mechanism toward lytic phages of the genus Kayvirus, mediated by the membrane-anchored protein designated PdpSau encoded by Staphylococcus aureus prophages, mostly of the Sa2 integrase type. The prophage accessory gene pdpSau is strongly linked to the lytic genes for holin and ami2-type amidase and typically replaces genes for the toxin Panton-Valentine leukocidin (PVL). The predicted PdpSau protein structure shows the presence of a membrane-binding α-helix in its N-terminal part and a cytoplasmic positively charged C terminus. We demonstrated that the mechanism of action of PdpSau does not prevent the infecting kayvirus from adsorbing onto the host cell and delivering its genome into the cell, but phage DNA replication is halted. Changes in the cell membrane polarity and permeability were observed from 10 min after the infection, which led to prophage-activated cell death. Furthermore, we describe a mechanism of overcoming this resistance in a host-range Kayvirus mutant, which was selected on an S. aureus strain harboring prophage 53 encoding PdpSau, and in which a chimeric gene product emerged via adaptive laboratory evolution. This first case of staphylococcal interfamily phage-phage competition is analogous to some other abortive infection defense systems and to systems based on membrane-destructive proteins. IMPORTANCE. Prophages play an important role in virulence, pathogenesis, and host preference, as well as in horizontal gene transfer in staphylococci. In contrast, broad-host-range lytic staphylococcal kayviruses lyse most S. aureus strains, and scientists worldwide have come to believe that the use of such phages will be successful for treating and preventing bacterial diseases. The effectiveness of phage therapy is complicated by bacterial resistance, whose mechanisms related to therapeutic staphylococcal phages are not understood in detail. In this work, we describe a resistance mechanism targeting kayviruses that is encoded by a prophage. We conclude that the defense mechanism belongs to a broader group of abortive infections, which is characterized by suicidal behavior of infected cells that are unable to produce phage progeny, thus ensuring the survival of the host population. Since the majority of staphylococcal strains are lysogenic, our findings are relevant for the advancement of phage therapy.
ER -
KUNTOVÁ, Lucie, Ivana MAŠLAŇOVÁ, Radka OBOŘILOVÁ, Hana ŠIMEČKOVÁ, Adéla FINSTRLOVÁ, Pavol BÁRDY, Marta ŠIBOROVÁ, Liudmyla TROIANOVSKA, Tibor BOTKA, Petr GINTAR, Ondrej ŠEDO, Zdeněk FARKA, Jiří DOŠKAŘ a Roman PANTŮČEK. Staphylococcus aureus Prophage-Encoded Protein Causes Abortive Infection and Provides Population Immunity against Kayviruses. \textit{mBio}. Washington, DC, USA: American Society for Microbiology, 2023, roč.~14, č.~2, s.~1-15. ISSN~2150-7511. Dostupné z: https://dx.doi.org/10.1128/mbio.02490-22.
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