Combination Utility Of Phages GH15and K Against The Infection Of Staphylococcus Aureus

Staphylococcus aureus (S. aureus) is a common and dangerous pathogen thatunderlies various infectious diseases. Treatment of these infections has become evermore difficult due to the increasing prevalence of multidrug-resistant strains,especially the emergence of methicillin-resistant strains, that are resistant to almost allcommon antibiotics except for Vancomycin. However, certain MRSA strains havealready acquired resistance to vancomycin as well. This situation aroused seriousconcerns within the medical community. Therefore, there is an urgent need for noveltherapeutic agents against this formidable pathogen.Phage could be an alternative to conventional antibiotic therapy againstpathogens that are resistant to multiple antibiotics.The advent of antibiotics in theearly stages had hindered the the development of phage therapy. However, the abusingof antibiotics has caused the appearance of resistant strains. Therefore, more andmore researchers began to re-examine the phage therapy and use phage to controlinfections caused by multidrug-resistant strains.However, high specificity of phage limits the phage therapy in the treatment ofbacterial infections. In contrast,“phage cocktail” can effectively “widen” the hostspectrum, thereby greatly improve its applicability. Recently, our lab have isolated anovel staphylococcal lytic phage, named GH15. In addition, the genome of GH15hasalso been sequenced and indicated that there is no virulent factor or protein associatedwith lysogenic. Otherwise, GH15shows high homologous with staphylococcal phageK in genomic level which also displayed broad host range.In the present report, the biological characteristics and the therapeutic potentialof the combination utility of GH15and K were determined. It indicated that the lengthof GH15tail was longer than that of K either in the state of contraction or non-shrinkcontraction by transmission electron microscopy. GH15shows the wider host range toS. aureus than K. GH15can lyse twenty-eight strains of tested S. aureus and K only kill seven strians. When a common host strain was infected by GH15and Krespectively, the sizes of plaques were different in diameter. When the common hoststrain was infected by GH15and K respectively, the proliferated trend of GH15wasdifferent from that of K by the fitting analysis of one step growth curve. The in vitrocracking experiments showed the stronger antibacterial activity of used cocktail(consisted of GH15and K) than used GH15or K alone to some strains. From the invivo experiment, the phage cocktail manifests effective protection against lethalinfection in mice. A single small dose injection of phage cocktail is sufficient toprotect mice effectively from fatal infection.Our results provide strong evidence towards the therapeutic use of phage cocktailas an alternative to antibiotics for acute infection caused by multidrug-resistant S.aureus.