Abstract
Bacteriophage therapy is considered one of the most promising therapeutic approaches against multi-drug resistant bacterial infections. Infections caused by Staphylococcus aureus are very efficiently controlled with therapeutic bacteriophage cocktails, containing a number of individual phages infecting a majority of known pathogenic S. aureus strains. We assessed the contribution of individual bacteriophages comprising a therapeutic bacteriophage cocktail against S. aureus in order to optimize its composition. Two lytic bacteriophages vB_SauM-515A1 (Myoviridae) and vB_SauP-436A (Podoviridae) were isolated from the commercial therapeutic cocktail produced by Microgen (Russia). Host ranges of the phages were established on the panel of 75 S. aureus strains. Phage vB_SauM-515A1 lysed 85.3% and vB_SauP-436A lysed 68.0% of the strains, however, vB_SauP-436A was active against four strains resistant to vB_SauM-515A1, as well as to the therapeutic cocktail per se. Suboptimal results of the therapeutic cocktail application were due to extremely low vB_SauP-436A1 content in this composition. Optimization of the phage titers led to an increase in overall cocktail efficiency. Thus, one of the effective ways to optimize the phage cocktails design was demonstrated and realized by using bacteriophages of different families and lytic spectra.
Highlights
Bacteriophage therapy is considered one of the most promising therapeutic approaches against multi-drug resistant bacterial infections
The wide spread of multidrug-resistant (MDR) bacterial pathogens is recognized by the World Health Organization (WHO) as a global threat to modern healthcare[1]
Therapeutic phage cocktails predominantly consist of a mixture of different bacteriophages directed against one or several bacterial s pecies[3]
Summary
Bacteriophage therapy is considered one of the most promising therapeutic approaches against multi-drug resistant bacterial infections. One promising alternative for the antibiotics to treat MDR infections is an approach that uses specific virulent bacteriophages as an antibacterial agent, known as phage therapy (PT). Most promising results are obtained with virulent phages of S. aureus[3,4,5] This pathogen causes different infectious processes (skin infection, toxin-related diseases, osteomyelitis, catheter-associated infection, and others) manifested by various symptoms ranging from relatively mild to life-threatening[6]. MRSA incidence, reported by 85 (44%) of the WHO member states, exceeds 20% and reaches as high values as 80% in some of these countries[7] For this reason, vancomycin became one of the first-line drugs to treat MRSA infections, but the clinical isolates of S. aureus with intermediate and complete resistance to vancomycin have emerged within the past two d ecades[8]. Linezolid and tedizolid can be used, but they have major side effects including thrombocytopenia, neuropathy, and even optic neuropathy[9]
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