Publication details

Spontaneous mutants of staphylococcal polyvalent bacteriophages with broad lytic host-range on Staphylococcus aureus strains are suitable for phage therapy



Year of publication 2017
Type Article in Proceedings
Conference 1st German Phage Symposium
MU Faculty or unit

Faculty of Science

Field Genetics and molecular biology
Keywords Bacteriophage; Spontaneous mutants; Specialized collections; Staphylococcus aureus; MRSA
Description Due to a high lytic activity and broad host range towards Staphylococcus aureus strains, the polyvalent Twort-like bacteriophages of genus Kayvirus, family Myoviridae represented by phage 812 are already used for phage therapy in the Czech Republic. From this phage spontaneous mutants can be isolated as rare plaques on resistant staphylococcal strains. Recently 15 phage mutants were characterized on genomic, proteomic and structural level. We determined their lytic effect on a set of 200 human and livestock-associated MRSA isolates. Phage 812 or its mutants were able to lyse 97 % of the MRSA livestock strains and 86 % of human MRSA strains. The lytic effect is preserved also in phage cocktails, therefore the novel mutants could be used for innovation of recent phage preparations in order to increase their effect on currently circulating strains. To assess the safety of phage 812 mutants for phage therapy, complete genome sequences were determined and compared to the wild-type phage 812. We have found that the mutants differ from the original genome mostly by short indels. Mutations seem to affect the host range in two ways: either interfere with adsorption genes (tail-fibre) and lysis (endolysin), or affect sequences that are the target of bacterial defence mechanisms such as RM-systems or CRISCP-Cas. Mutations do not induce lysogenic conversion and transduction nor virulence factors production. Therefore, the mutants thus obtained can be considered safe for phage therapy. Acknowledgement: Research was supported by a grant of Ministry of Agriculture of the Czech Republic No. QJ1510216.
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