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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.
Highlights
The M. abscessus complex is a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria (NTM) that are responsible for a wide spectrum of lung, skin, and soft tissue diseases; central nervous system and ocular infectious diseases; and bacteremia in both healthy and immunocompromised individuals [1]
Phage therapy is a promising alternative to combat superbugs, such as members of the M. abscessus complex; we still need to improve the efficiency of the phages by increasing their host-range and their lytic activity, using available cutting-edge genetic engineering tools
Bacteriophage Recombineering of Electroporated DNA (BRED) has been applied to genome editing of mycobacteriophages before and could be considered as short-term solution for the manipulation of the mycobacteriophages; editing through CRISPR, rebooting and arming mycobacteriophages should be considered as a long-term solution to increase the application of phage therapy against the M. abscessus complex
Summary
The M. abscessus complex is a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria (NTM) that are responsible for a wide spectrum of lung, skin, and soft tissue diseases; central nervous system and ocular infectious diseases; and bacteremia in both healthy and immunocompromised individuals [1]. It has been reported that macrolidecontaining regimens resulted in sputum culture conversion only in 34% and 54% of the new M. abscessus subsp. M. abscessus is resistant to most classes of antibiotics, including macrolides, aminoglycosides, rifamycins, tetracyclines, and β-lactams [4]; as a result, there are a wide range of treatment strategies for M. abscessus infection using prolonged antimicrobial drug therapy, with significant side effects, and therapies often need to be Microorganisms 2021, 9, 596. Abscessus complex, require new approaches beyond routine antibiotic therapy. To combat multidrug-resistant (MDR) bacteria such as M. abscessus, breakthrough strategies that go beyond classical antibiotic mechanisms are urgently needed.
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