Novel spontaneous mutants of bacteriophage 812 exhibit multiple
genomic changes and increased lytic effect on MRSA strains

a 2018

Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains

BOTKA, Tibor, Roman PANTŮČEK, Martin BENEŠÍK, Vladislava RŮŽIČKOVÁ, Ivana KOLÁČKOVÁ et. al.

Základní údaje

Originální název

Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains

Autoři

BOTKA, Tibor (203 Česká republika, garant, domácí), Roman PANTŮČEK (203 Česká republika, domácí), Martin BENEŠÍK (203 Česká republika, domácí), Vladislava RŮŽIČKOVÁ (203 Česká republika, domácí), Ivana KOLÁČKOVÁ (203 Česká republika) a Jiří DOŠKAŘ (203 Česká republika, domácí)

Vydání

EMBO Workshop | Viruses of Microbes 2018 Abstract Book: 09 - 13 July 2018 | Wroclaw, Poland, 2018

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10607 Virology

Stát vydavatele

Polsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14310/18:00100667

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

MRSA; Kayvirus; host-range mutants; lytic phages; Staphylococcus

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 3. 2019 14:19, prof. RNDr. Roman Pantůček, Ph.D.

Anotace

V originále

The phage therapy, an alternative to fight against methicillin-resistant Staphylococcus aureus (MRSA) strains, requires precise genome evaluation of used phages to ensure its efficiency and safety. Bacteriophages of the genus Kayvirus are commonly used in phage preparations. However, it is necessary to adapt the phage composition to be effective against emerging phage-resistant strains. The evolutionary “training” under laboratory conditions was used to obtain phages with extended host range. We focused on phage 812, characterized by a high lytic activity and a broad host range towards staphylococcal strains. Five phage 812-derived mutants were selected on strains insusceptible to the wild type. The lytic ability of the phages was tested on the set of 94 human and 92 veterinary MRSA strains. The mutant 812h1 showed the highest lytic activity when lysing 82 % of human and 97 % of veterinary strains. The causes of the phage host-range changes were investigated by comparative genomic analysis of the phage mutants. We found interspersed and tandem direct repeats of various motifs differing in copy number and genome location that served as hot-spots for rearrangements creating multiple genomic variants. Mutations specific for each host-range mutant were characterized. Genes for nucleic acid metabolism, tail tube protein and endolysin were affected. Genome of 812h1 contains regions gained from other strains of Kayvirus genus suggesting possible recombination events. Although the selection strains carried prophages and plasmids, no studied mutant contained genes of such origin as well as genes for antibiotic resistance or bacterial virulence. The results of our study demonstrate, that genomic changes observed in spontaneous host-range mutants do not possess any risk for the therapeutic use. This work was supported by Grant of Czech Ministry of Agriculture (QJ1510216), and Czech Science Foundation (GA18-13064S).

Návaznosti

GA18-13064S, projekt VaV

Název: Analýza interakcí mezi polyvalentním terapeutickým fágem druhu Twort-like a jeho hostitelem Staphylococcus aureus

Investor: Grantová agentura ČR, Analýza interakcí mezi polyvalentním terapeutickým fágem druhu Twort-like a jeho hostitelem Staphylococcus aureus

QJ1510216, projekt VaV

Název: Fágová terapie infekcí vyvolaných Staphylococcus aureus v chovech hospodářských zvířat (Akronym: StafyFag)

Investor: Ministerstvo zemědělství ČR, Fágová terapie infekcí vyvolaných Staphylococcus aureus v chovech hospodářských zvířat

Citovat

BOTKA, Tibor, Roman PANTŮČEK, Martin BENEŠÍK, Vladislava RŮŽIČKOVÁ, Ivana KOLÁČKOVÁ a Jiří DOŠKAŘ. Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains. In EMBO Workshop | Viruses of Microbes 2018 Abstract Book: 09 - 13 July 2018 | Wroclaw, Poland. 2018.

@proceedings{1423678,
   author = {Botka, Tibor and Pantůček, Roman and Benešík, Martin and Růžičková, Vladislava and Koláčková, Ivana and Doškař, Jiří},
   booktitle = {EMBO Workshop | Viruses of Microbes 2018 Abstract Book: 09 - 13 July 2018 | Wroclaw, Poland},
   keywords = {MRSA; Kayvirus; host-range mutants; lytic phages; Staphylococcus},
   language = {eng},
   title = {Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains},
   url = {http://meetings.embo.org/event/18-virus-microbe},
   year = {2018}
}

TY  - CONF
ID  - 1423678
AU  - Botka, Tibor - Pantůček, Roman - Benešík, Martin - Růžičková, Vladislava - Koláčková, Ivana - Doškař, Jiří
PY  - 2018
TI  - Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains
KW  - MRSA
KW  - Kayvirus
KW  - host-range mutants
KW  - lytic phages
KW  - Staphylococcus
UR  - http://meetings.embo.org/event/18-virus-microbe
N2  - The phage therapy, an alternative to fight against methicillin-resistant Staphylococcus aureus (MRSA) strains, requires precise genome evaluation of used phages to ensure its efficiency and safety. Bacteriophages of the genus Kayvirus are commonly used in phage preparations. However, it is necessary to adapt the phage composition to be effective against emerging phage-resistant strains. The evolutionary “training” under laboratory conditions was used to obtain phages with extended host range. We focused on phage 812, characterized by a high lytic activity and a broad host range towards staphylococcal strains. Five phage 812-derived mutants were selected on strains insusceptible to the wild type. The lytic ability of the phages was tested on the set of 94 human and 92 veterinary MRSA strains. The mutant 812h1 showed the highest lytic activity when lysing 82 % of human and 97 % of veterinary strains. The causes of the phage host-range changes were investigated by comparative genomic analysis of the phage mutants. We found interspersed and tandem direct repeats of various motifs differing in copy number and genome location that served as hot-spots for rearrangements creating multiple genomic variants. Mutations specific for each host-range mutant were characterized. Genes for nucleic acid metabolism, tail tube protein and endolysin were affected. Genome of 812h1 contains regions gained from other strains of Kayvirus genus suggesting possible recombination events. Although the selection strains carried prophages and plasmids, no studied mutant contained genes of such origin as well as genes for antibiotic resistance or bacterial virulence. The results of our study demonstrate, that genomic changes observed in spontaneous host-range mutants do not possess any risk for the therapeutic use. This work was supported by Grant of Czech Ministry of Agriculture (QJ1510216), and Czech Science Foundation (GA18-13064S).
ER  -

BOTKA, Tibor, Roman PANTŮČEK, Martin BENEŠÍK, Vladislava RŮŽIČKOVÁ, Ivana KOLÁČKOVÁ a Jiří DOŠKAŘ. Novel spontaneous mutants of bacteriophage 812 exhibit multiple genomic changes and increased lytic effect on MRSA strains. In \textit{EMBO Workshop $|$ Viruses of Microbes 2018 Abstract Book: 09 - 13 July 2018 $|$ Wroclaw, Poland}. 2018.

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