Population changes of heteroresistant Mycobacterium tuberculosis harbouring rare resistance-conferring mutations in gyrA and rpoB implies an epistatic interaction of the mutations related to strain fitness in pre-XDR-TB patient. Mycobacterium tuberculosis strain:strain

The goals of this study is to unveil the genomic factors underlying the uniqueness of this clinical case which is highlighted as follows: 1) the acquisitions of RIF-resistant genotypes (rpoB V170F) occurred under a multi-drug therapy after exclusion of RIF, 2) the sub-clone which harbors rare resistant conferring mutations, rpoB V170F and gyrA S91P, rapidly outcompeted others (< 7days) under the treatment including LVFX but not RIF, 3) once the sub-clone dominated the population, it retained as dominant clone even after stopping LVFX and revised regimens with DLM, LZD, TH, and CS, 4) HCM rpoC V483A emerged and became dominant under the RIF free treatment.