Novel methods to design wild bacteriophages into highly lytic and therapeutic bacteriophages to extensively drug-resistant Mycobacterium tuberculosis

Background: The emergence of multiple drug resistant (MDR) Mycobacterium tuberculosis (M.TB) and extensive drug resistant (XDR) M.TB lay huge burden on TB endemic countries such as Iraq. Objectives: Bacteriophage (phage) therapy can be used as alternative approach to tackle this problem. Patients and methods: Forty isolates of M.TB were cultured from TB-positive sputum specimens with three ATCC strains. Phage passaging and biokinetic based techniques were used to optimize wild anti-M.TB phages. Three chemical, non genetic- designing techniques, tween-80, mycobacterial lysis buffer, and xyelen, were used to change the specificity of wild anti-TB phages towards phage-resistant target M.TB. Results: Five wild anti-M.TB phages were isolated and optimized. The optimization techniques were successful in enhancing plaques size, clarity, burst size, and infective ratio. Chemical designing techniques succeeded to reorient specificity of 6 phages to new host bacteria. Conclusions: phage designing opens door wide for endless future applications of phage-based therapy, biocontrol and diagnosis.