Phage cocktail as wonderful bio-nanoparticles for theprophylaxis and treatment of burn wound infection caused bymultidrug-resistant bacteria in a mouse model.

Background and Aim : Multi-drug resistance has become a major problem for the treatment ofpathogenic bacterial infections. The use of bacteriophages is an attractive approach to overcomethe problem of drug resistance in pathogens that cause fatal infections. Our study aimed to collectmethicillin resistance Staphylococcus aureus and multi drug resistant Pseudomonas aeruginosaand Acinetobacter baumannii from patients with burn wounds and then isolate specific lyticbacteriophages against these pathogens. Then apply their cocktail as alternative therapeutic agentsin a mouse model of mixed infection.Methods : MDR-bacterial strains were collected from the microbiology laboratory of Motaharihospital. Bacteriophages were isolated from hospital sewage by double-layer agar method andtested in vitro for lytic activity against resistant isolates as well as some biological features.Morphological characteristics were identified by transmission electron microscopy (TEM). Theisolated phages were named ΦS۱, ΦPsd۱sw, and ΦA۱sw for lytic phage of methicillin-resistantStaphylococcus aureus and multi-drug resistant Pseudomonas aeruginosa and Acinetobacterbaumannii respectively. We also examined the therapeutic potential of ΦS۱, ΦPsd۱sw, andΦA۱sw Bacteriophages cocktail for prophylaxis and treatment of mixed bacterial infection in۵groups of Six-week-old male Swiss mice (weight ∼۲۵-۳۰ g per mouse) during ۱۴ days by colonycounting method.Results : Morphological identification of ΦS۱, ΦPsd۱sw, and ΦA۱sw Phages by transmissionelectron microscopy showed that these virion particles belonged to Myoviridae (ΦS۱) andsiphoviridae (ΦPsd۱sw and ΦA۱sw) family, with clear plaques without halo that demonstrate thelytic activity of isolated phages. In this study, the administration of a phage cocktail within onedose could prevent (group I: before bacterial infection) and treat (group II: after bacterial infection)mixed bacterial infection in comparison with control groups (almost ten-fold decrease in colonycount number). Our data also demonstrated that administration of two-dose (one dose day۱ andone dose on day ۸ after infection) phage cocktails may be more effective prophylaxis and treatmentfor mixed infection than one dose cocktail (۵ fold decrease).Conclusion : In vitro and in vivo analysis of the phage cocktail demonstrated perfect lysis againstthe corresponding MDR-bacteria, and this cocktail may be promising as the first choice forprophylaxis against wound infection. Hence, our results suggest that this bacteriophage cocktailcould be a potential therapeutic option for treating septic wounds caused by S. aureus, P.aeruginosa, and A.baumannii.

کلیدواژه ها:

MDR ، bacteriophage ، phage cocktail ، S. aureus ، P. aeruginosa ، A.baumannii.