Experimental Phage Therapy Against Staphylococcus Aureus-induced Burn Wound Infection In Mice

Staphylococcus aureus is the main pathogen causing burn wound infection.The increasing prevalence of antibiotic resistance in clinical isolates of Staphylococcus aureus poses a dilemma in controlling Staphylococcal infection.Phages are viruses that specifically infect bacteria.Phage therapy is a method of using phages as bioagents for the treatment of bacterial infectious diseases.ObjectiveThe main goal of this study was to evaluate the efficiency of phage therapy against S.aureus infection in murine burn wound.At the same time,the phage genome was sequenced and analyzed to provide a preliminary basis for the safe application of phage therapy in bacterial infectious diseases.MethodWhen burned animals were injected subcutaneously with different concentrations of S.aureus,the minimum lethal dose of bacteria that can cause all animal deaths was obtained.After infecting burned animals with the minimum lethal dose of bacteria,the animals were treated with bacteriophages through different routes(subcutaneous,intraperitoneal and intramuscular)and the survival rate was observed.The phage genome was sequenced using the Liiumina HiseqPE150 platform,and the sequenced genome was subjected to gene prediction by GeneMarkS software.ResultsMice compromised by a burn wound injury and subjected to a minimum lethal dose of S.aureus were administrated a single dose of phage at MOI of 10(1×10~111 PFU/mL)by three different routes.The results of these studies indicated that the survival rate of untreated control mice was 23.8%and the survival rate of mice treated with phages subcutaneously or intraperitoneally was 66.7%62.0%,respectively.The survival rate of mice treated with phages by intramuscular route was only 23.8%.It suggested that phages exhibited therapeutic value in treating wound infection in mice and the route of administration was particularly crucial to the efficacy of the treatment,with subcutaneous and intraperitoneal route providing the most significant protection(P<0.025).The phage(HYZ21)genome had a full length of 139,675 bp,a G+C content of30.42%,and 208 coding genes and 4 tRNA genes.Conclusion The phage HYZ21 has obvious protective effects on burn wound animals infected by S.aureus,suggesting the potential use of phage for control burn wound infection.Phage HYZ21 belongs to the genus Kayvirus,family Myoviridae,order Caudovirales.