1 Drug susceptible TB Limited resistance MDR-TB (Frieden, 1993) XDR-TB (Alexander and De, 2007) Total DR (Velayati, et al., 2009) Resistance to 1st line anti-TB drugs Rifampicin, Isoniazid Resistance to 2nd line anti-TB drugs Fluoroquinolone, Injectable drugs: Kanamycin, Capreomycin, Amikacin Resistance to all available anti-TB drugs Treatable with 1st line anti-TB drugs Isoniazid, Pyrazinamide, Ethambutol Treatable with 2nd line anti-TB drugs Treatment options seriously restricted No treatment options Fig.1 1

a b d c Drug efflux pump Drug target Drug degrading enzyme Drug inactivating enzyme Fig.2

PDIM Heme MBT cMBT Econazole SL-1 INH Mycolate wax ester Glycophospholipid MmpL3 MmpL4 MmpL5 MmpL7 MmpL8 MmpL11 Cell Membrane TMM Fig.3

Mycobacterium abscessus TMM AU1235 SQ109 BM212 Indolcarboxamide Spiro THPP PIPD MmpL3 Mycobacterium abscessus Mtb Fig.4

Drug efflux Iron acquisition Lipid transport Death of bacterium Fig.5