Phage Therapy for Mycobacterium Abscessus and Strategies to Improve Outcomes

Abstract

Members of Mycobacterium abscessus complex are known for causing severe, chronic infections. Members of M. abscessus are a new “antibiotic nightmare” as one of the most resistant organisms to chemotherapeutic agents. Treatment of these infections is challenging due to the either intrinsic or acquired resistance of the M. abscessus complex to the available antibiotics. Recently, successful phage therapy with a cocktail of three phages (one natural lytic phage and two engineered phages) every 12 h for at least 32 weeks has been reported against a severe case of the disseminated M. abscessus subsp. massiliense infection, which underlines the high value of phages against drug-resistant superbugs. This report also highlighted the limitations of phage therapy, such as the absence of lytic phages with a broad host-range against all strains and subspecies of the M. abscessus complex and also the risk of phage resistant bacteria over treatment. Cutting-edge genomic technologies have facilitated the development of engineered phages for therapeutic purposes by introducing new desirable properties, changing host-range and arming the phages with additional killing genes. Here, we review the available literature and suggest new potential solutions based on the progress in phage engineering that can help to overcome the present limitations of M. abscessus treatment.