Considerations for Phage Therapy Against Mycobacterium abscessus

Abstract

There is a global increasing number of Mycobacterium abscessus infections, especially pulmonary infections. Reduced therapeutic options exist against this opportunistic pathogen due to its high intrinsic and acquired levels of antibiotic resistance. Phage therapy is a promising afresh therapy, which uses viruses to lyse bacteria responsible for the infection. Bacteriophages have been recently administered under compassionate use to a 15-year-old patient infected with M. abscessus in combination with antibiotics with excellent results. This mini review highlights different recommendations for future phage administrations such as where to look for new phages, the use of cocktail of mycobacteriophages to broaden phage specificity and to tackle resistance and phage insensitivity due to temperate phages present in bacterial genomes, the combined use of phages and antibiotics to obtain a synergistic effect, the liposomal administration to reach a prolonged effect, intracellular delivery and protection against neutralizing antibodies, and the convenience of using this strategy in patients suffering from cystic fibrosis (CF) since phages are believed to promote immunomodulatory actions and eliminate biofilms.

Mycobacteriophage–antibiotic therapy promotes enhanced clearance of drug-resistant Mycobacterium abscessus

“…In this case, the therapy resulted in decreased size of skin lesions and improvement in lung function, liver function, chest imaging and weight gain. Although this illustrates that phage therapy against NTM infections holds vast potential, there is little understanding of phage-host dynamics in disease environments and a clear lack of pre-clinical studies concerning phage therapy of M. abscessus infections (Senhaji-Kacha et al, 2021). In this context, we studied the GD01mycobacteriophage infection dynamics under various physiological and disease-mimicking conditions using a CF zebrafish model of infection.…”

A Review on Mycobacteriophages: From Classification to Applications

“…In 2021, the result of a clinical trial on a patient with cystic fibrosis (CF) suffering from a prolonged disseminated infection with M. abscessus , Pseudomonas aeruginosa, EBV viremia (8 years), with a history of two lung transplantations along with administration of various oral/intravenous antibiotics, lumacaftor/ivacaftor, and immunosuppressive drugs (e.g., Clofazimine, bedaquiline, Mycophenolate mofetil, iv rituximab) revealed that the hypodermic administration of mycobacteriophages cocktail containing Muddy (wild type) and engineered BPs33ΔHTH-HRM10 and ZoeJΔ45 every 12 h for seven months (10 9 pfu/dose of each phage) could improve the recovery in this patient [ 16 , 17 , 196 ]. Furthermore, regarding the engineered phages used in the recent study, repressors that induce the lysogenic life cycle in these phages were deleted, and these phages were converted to lytic phages.…”

“…Furthermore, regarding the engineered phages used in the recent study, repressors that induce the lysogenic life cycle in these phages were deleted, and these phages were converted to lytic phages. Accordingly, this analysis indicated that the application of mycobacteriophage cocktails could resolve problems caused by phage-resistant M. abscessus strains and temperate phages that were previously integrated into the bacterial genome and contributed to expanding the infection [ 17 ].…”

“…Today, mycobacteriophages in isolation/cocktail [ 15 ] or within a synergistic therapy along with antibiotics opened new horizons in the treatment of infections caused by pathogenic mycobacteria [ 16 , 17 , 18 ]. Furthermore, mycobacteriophages have been exploited in diagnostic approaches of slow-/fast-growing mycobacteria through shuttle plasmids that express resistance against antibiotics and induce the production of lysogenic plaques in target mycobacteria [ 19 ]; transduction of nanoluciferase reporter gene cassettes that discriminate viable drug-resistant and -sensitive strains [ 20 ]; phage amplification for detection of antimicrobial resistance species [ 21 , 22 , 23 ]; and viability assessment of target mycobacteria in various samples (i.e., dairy products, blood, stool [ 24 , 25 ]).…”

Insertion Mutation of MSMEG_0392 Play an Important Role in Resistance of M. smegmatis to Mycobacteriophage SWU1

“…Bacteriophage is a potential tool in the treatment of bacterial infection, rapid detection of pathogens, bacterial typing, control of bacterial contamination in food, treatment of environmental pollution, control of pathogen transmission and molecular biology research. [7][8][9][10][11][12][13][14] It has been reported that bacteriophages are used to treat Mycobacterium infections, for example, in 2019, the United States researchers clinically improved one case of cystic fibrosis with disseminated mycobacterial infection by intravenous injection of three mycobacterial bacteriophages. 15 In addition, bacteriophages also have been reported for the treatment of Carbapenem-Resistant Klebsiella pneumoniae, [16][17][18][19] multidrug-resistant Acinetobacter baumannii, 20 pan-drug resistant Pseudomonas aeruginosa et al 21 But we cannot be too blindly optimistic, because we have to face the reality that bacteria are resistant to bacteriophages.…”