Figure 1

Time-line of clinical interventions and drug resistance acquisition. Drug regimen is indicated by horizontal bars. Black dashed lines indicate available clinical isolates. Above the dashed lines, the first instances of resistance-conferring mutations identified in the corresponding clinical isolates are indicated. The mutations are colored to match the drug to which it confers resistance. Black boxes indicate mutations that were ultimately fixed (>85% of reads in SF9), whereas non-boxed mutations indicate transient mutations. INH, isoniazid; RIF, rifampicin; PZA, pyrazinamide; EMB, ethambutol; STR, streptomycin; OFX, ofloxacin; ETH, ethionamide; CFZ, clofazimine; AMK, amikacin; AMC, amoxicillin/clavulanate; LVX, levofloxacin; GFB, gemfibrozil; IFNγ, gamma interferon; CPR, capreomycin; LZD, linezolid. Frameshift mutations are denoted as fs.