The mechanisms by which drug resistance emerges and is
fixated in M.tb populations are not wholly understood (Table 1). In
vitro studies have identified several determinants of resistance to
the main anti-TB drugs, but whole-genome analyses suggest that
the response to drug exposure might be much more complex than
initially thought and involve a set of strategies developed by
mycobacteria to enhance their ability to adapt and evolve.
Furthermore, there are indications that the acquisition of clinically
significant resistance to certain drugs might be a stepwise process
that often involves an initial low-level mutation that acts as a
gateway for high-level resistance. The clinical implications of these
findings should be investigated