A mouse air pouch model for evaluating the anti-bacterial efficacy of phage MR-5 in resolving skin and soft tissue infection induced by methicillin-resistant Staphylococcus aureus.

Abstract

With the alarming rise in antimicrobial resistance, phage therapy represents a new paradigm for combating antibiotic-resistant infectious diseases that is worth exploring for its clinical success. With this scenario, the present study aimed at evaluating the in vivo potential of phage MR-5 (broad host range Staphylococcus aureus phage) against soft tissue infections induced by methicillin-resistant S. aureus (MRSA). Also, the usefulness of relatively simple murine air pouch as a dual-purpose model (to study both anti-bacterial and anti-inflammatory parameters) in the field of phage therapeutics has been put to test. Murine air pouch model was established with experimental skin infection induced by S. aureus ATCC 43,300 followed by subcutaneous administration of phage alone as well as along with linezolid. Phage MR-5 alone and incombination with linezolid (showing synergy) brought significant reduction in the bacterial load (both extracellular as well as intracellular) that led to faster resolution of pouch infection. The main conclusions surfaced from the present study include the following: (a) murine air pouch model represents a simple useful model (mimicking subcutaneous skin infection) for studying anti-bacterial potencies of drug candidates. Therefore, its use and further adaptations especially in field of phage therapeutics is highly advocated and (b) phage MR-5 proved to be a potential therapeutic candidate against treatment of MRSA-induced skin and soft tissue infections and use of combination therapy is stronglyrecommended.