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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00100667" target="_blank" >RIV/00216224:14310/18:00100667 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

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

Original language description

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).

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10607 - Virology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2018

Confidentiality

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