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High genome variability within Kayvirus populations is key to improving their therapeutic efficacy against staphylococci

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BOTKA Tibor PANTŮČEK Roman BENEŠÍK Martin DOŠKAŘ Jiří

Rok publikování 2019
Druh Článek ve sborníku
Konference 8th International Weigl Conference: HUMAN WELFARE AND INFECTIOUS DISEASES IN A NEW MICROBIOME RESEARCH ERA
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www 8th International Weigl Conference
Popis Lytic bacteriophages are used as alternative therapeutics against bacterial infections. To overcome phage resistance of some pathogens, new phages are isolated from the environment or using phage training. Another approach, based on isolation of rare single plaques of spontaneous mutants grown on phage resistant strains of S. aureus, was used to obtain five kayvirus 812 mutants. The host range of this set of mutants was 42% higher than the wild type, determined on 186 MRSA strains. Genomes of the phage mutants were investigated by deep sequencing. It revealed that some polymorphisms from the parental phage population were fixed in next-step mutants, mostly in genes for tail and baseplate components associated with host range. Genome of the most effective multi-step mutant 812h1 was highly variable due to polymorphisms associated with rearrangements between repeated sequences resulted in alterations in host-takeover and terminal genomic regions. Some regions of 812h1 genome were distinct from the wild-type phage but the corresponding sequences were found in its sequencing data with very low coverage. These results suggest that a large pool of phage sequences is maintained in minor genome variants persisting in Kayvirus populations. The high prevalence of polymorphisms in phage genomes indicates a high mutation rate that results in rapid diversification of the phage populations and enables us to isolate phage mutants effective against broad range of staphylococcal strains. This work was supported by grants from the Czech Science Foundation (18-13064S).
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