LUCIFERASE REPORTER MYCOBACTERIOPHAGES FOR EVALUATING NORBORNENE-BASED ANTITUBERCULOSIS DRUG SUSCEPTIBILITY TESTING ON MYCOBACTERIUM TUBERCULOSIS

Abstract

Objective: In 2015, 9.6 million people around the world became sick with tuberculosis (TB) disease and 1.5 million TB-related deaths worldwide. Recent increasing incidence of multidrug-resistant (MDR; resistance to at least rifampicin (RIF) and isoniazid [INH]) and extensively drug-resistant (MDR resistance plus resistance to a fluoroquinolone and an aminoglycoside) makes TB a serious concern. Lot of research is needed to deal with this infectious disease for a better alternative in treatment or modification of these older TB drugs. The present study aimed at evaluating antimycobacterial activity of norbornene (NOR) derived INH copolymer with poly ethylene glycol (NOR- polyethylene glycol [PEG]-INH) a novel nanocarrier along with the anti-TB drug using luciferase reporter phages (LRPs).Methods: NOR derived INH accounts for 74% of INH, 24% of NOR, and 2% of PEG. H37Rv control strain, a sensitive, and a resistant strain of Mycobacterium TB (MTB) used in this study. The in vitro activity of the drug was evaluated using absolute concentration method. The resistant strain was evaluated using LRP assay to observe the minimum inhibitory concentration of the drug.Results: Reduction in light units was observed for the resistant strain exposed to plain INH and NOR-PEG-INH separately. 24% of reduction was observed in strains exposed to plain INH whereas 37% of reduction was observed in strains exposed to NOR-PEG-INH.Conclusion: NOR-based INH had better antimycobacterial activity compared to plain INH and RIF. Antimycobacterial activity of INH and RIF increases even with very low dosage with NOR conjugate.