Isolation and characterization of compound-resistant isolates of Mycobacterium tuberculosis.

This chapter describes the isolation and characterization of spontaneous resistant mutants of Mycobacterium tuberculosis. The overall objective of resistant mutant isolation is to determine the mode of action and/or cellular targets of new antimycobacterial agents. Whole-genome sequencing of resistant mutants can identify targets of antimycobacterial drugs and mechanisms of resistance, such as efflux, changes in drug permeability, or drug recognition. Mutants allow insight into in vivo biological processes and can help elucidate the number and identity of genes in a given pathway. Resistant mutant characterization can also lay the groundwork for structure/function studies, especially in conjunction with binding studies and X-ray crystallography.