**6. Conclusion**

The idea that the DR phenotype is determined by multiple genes was supported in a review by Trauner *et al*. and Müller *et al*. [9, 13]. They argued that the genetic background of Mtb is important in determining the phenotypic effect of DR mutations. Epistasis—the genetic interactions that determine a phenotype—and bacterial fitness are the two factors that determine the evolution of drug resistance. It is thus important to study genes that are directly involved in drug metabolism as well as genes that could play a compensatory role, such as those involved in aspects of cell physiology, e.g., permeability of the cell. The complexity of the genetic and epistatic determination of the DR phenotype allows the development of new drugs to induce reversion of drug resistance in populations of pathogens. The phenomenon of DR reversion was defined in a review by Baym *et al*. as an active drug-induced counterselection of resistant variants from populations of pathogens [37]. Several theoretical assumptions were discussed in this paper to explain the resistance reversion despite the presence of selective antibiotics in a medium. Practical application of the antibiotic resistance reversion approach to combat multidrug resistant tuberculosis was exemplified in this work by an overview of the clinical trial of the new drug FS-1.

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