66. Gurcha SS, Usha V, Cox JA, Futterer K, Abrahams KA, Bhatt A, Alderwick LJ,
Reynolds RC, Loman NJ, Nataraj V, Alemparte C, Barros D, Lloyd AJ, Ballell L,
Hobrath JV, Besra GS (2014) Biochemical and structural characterization of mycobacterial
aspartyl-tRNA synthetase AspS, a promising TB drug target. PLoS ONE 9:e113568
67. Soto R, Perez-Herran E, Rodriguez B, Duma BM, Cacho-Izquierdo M, Mendoza-Losana A,
Lelievre J, Aguirre DB, Ballell L, Cox LR, Alderwick LJ, Besra GS (2018) Identification
and characterization of aspartyl-tRNA synthetase inhibitors against Mycobacterium tuberculosis by an integrated whole-cell target-based approach. Sci Rep 8:12664
68. Palencia A, Li X, Bu W, Choi W, Ding CZ, Easom EE, Feng L, Hernandez V, Houston P,
Liu L (2016) Discovery of novel oral protein synthesis inhibitors of Mycobacterium
tuberculosis that target leucyl-tRNA synthetase. Antimicrob Agents Chemother 6271–6280
69. Rock FL, Mao W, Yaremchuk A, Tukalo M, Crépin T, Zhou H, Zhang Y-K, Hernandez V,
Akama T, Baker SJ (2007) An antifungal agent inhibits an aminoacyl-tRNA synthetase by
trapping tRNA in the editing site. Science 316:1759–1761
70. Abrahams KA, Cox JA, Spivey VL, Loman NJ, Pallen MJ, Constantinidou C, Fernandez R,
Alemparte C, Remuinan MJ, Barros D (2012) Identification of novel imidazo [1, 2-a]
pyridine inhibitors targeting M. tuberculosis QcrB. PloS one 7:e52951
71. Moraski GC, Seeger N, Miller PA, Oliver AG, Boshoff HI, Cho S, Mulugeta S,
Anderson JR, Franzblau SG, Miller MJ (2016) Arrival of imidazo [2, 1-b] thiazole-5carboxamides: potent anti-tuberculosis agents that target QcrB. ACS Infect Dis 2:393–398
72. Chandrasekera NS, Berube BJ, Shetye G, Chettiar S, O’Malley T, Manning A, Flint L,
Awasthi D, Ioerger TR, Sacchettini J (2017) Improved phenoxyalkylbenzimidazoles with
activity against Mycobacterium tuberculosis appear to target QcrB. ACS Infect Dis 3:898–
916
73. McKinney JD, Zu Bentrup KH, Muñoz-Elías EJ, Miczak A, Chen B, Chan W-T,
Swenson D, Sacchettini JC, Jacobs WR Jr, Russell DG (2000) Persistence of Mycobacterium
tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase.
Nature 406:735–738
74. Muñoz-Elías EJ, McKinney JD (2005) Mycobacterium tuberculosis isocitrate lyases 1 and 2
are jointly required for in vivo growth and virulence. Nat Med 11:638–644
75. Huang H-L, Krieger IV, Parai MK, Gawandi VB, Sacchettini JC (2016) Mycobacterium
tuberculosis malate synthase structures with fragments reveal a portal for substrate/product
exchange. J Biol Chem 27421–27432
76. Krieger IV, Freundlich JS, Gawandi VB, Roberts JP, Gawandi VB, Sun Q, Owen JL,
Fraile MT, Huss SI, Lavandera J-L (2012) Structure-guided discovery of phenyl-diketo acids
as potent inhibitors of M. tuberculosis malate synthase. Chem Biol 19:1556–1567
77. Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs J-M, Winkler H, Van Gestel J,
Timmerman P, Zhu M, Lee E (2005) A diarylquinoline drug active on the ATP synthase of
Mycobacterium tuberculosis. Science 307:223–227
78. Kundu S, Biukovic G, Grüber G, Dick T (2016) Bedaquiline targets the subunit of
mycobacterial F-ATP synthase. Antimicrob Agents Chemother 6977–6979
79. Pethe K, Bifani P, Jang J, Kang S, Park S, Ahn S, Jiricek J, Jung J, Jeon HK, Cechetto J
(2013) Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat
Med 19:1157–1160
80. Bryk R, Arango N, Venugopal A, Warren JD, Park Y-H, Patel MS, Lima CD, Nathan C
(2010) Triazaspirodimethoxybenzoyls as selective inhibitors of mycobacterial lipoamide
dehydrogenase. Biochemistry 49:1616–1627
81. Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C (2011)
Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member
of three multienzyme complexes. Cell Host Microbe 9:21–31
82. Tullius MV, Harth G, Horwitz MA (2003) Glutamine synthetase GlnA1 is essential for
growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs.
Infect Immun 71:3927–3936
Impact of Target-Based Drug Design in Anti-bacterial …
341
Reynolds RC, Loman NJ, Nataraj V, Alemparte C, Barros D, Lloyd AJ, Ballell L,
Hobrath JV, Besra GS (2014) Biochemical and structural characterization of mycobacterial
aspartyl-tRNA synthetase AspS, a promising TB drug target. PLoS ONE 9:e113568
67. Soto R, Perez-Herran E, Rodriguez B, Duma BM, Cacho-Izquierdo M, Mendoza-Losana A,
Lelievre J, Aguirre DB, Ballell L, Cox LR, Alderwick LJ, Besra GS (2018) Identification
and characterization of aspartyl-tRNA synthetase inhibitors against Mycobacterium tuberculosis by an integrated whole-cell target-based approach. Sci Rep 8:12664
68. Palencia A, Li X, Bu W, Choi W, Ding CZ, Easom EE, Feng L, Hernandez V, Houston P,
Liu L (2016) Discovery of novel oral protein synthesis inhibitors of Mycobacterium
tuberculosis that target leucyl-tRNA synthetase. Antimicrob Agents Chemother 6271–6280
69. Rock FL, Mao W, Yaremchuk A, Tukalo M, Crépin T, Zhou H, Zhang Y-K, Hernandez V,
Akama T, Baker SJ (2007) An antifungal agent inhibits an aminoacyl-tRNA synthetase by
trapping tRNA in the editing site. Science 316:1759–1761
70. Abrahams KA, Cox JA, Spivey VL, Loman NJ, Pallen MJ, Constantinidou C, Fernandez R,
Alemparte C, Remuinan MJ, Barros D (2012) Identification of novel imidazo [1, 2-a]
pyridine inhibitors targeting M. tuberculosis QcrB. PloS one 7:e52951
71. Moraski GC, Seeger N, Miller PA, Oliver AG, Boshoff HI, Cho S, Mulugeta S,
Anderson JR, Franzblau SG, Miller MJ (2016) Arrival of imidazo [2, 1-b] thiazole-5carboxamides: potent anti-tuberculosis agents that target QcrB. ACS Infect Dis 2:393–398
72. Chandrasekera NS, Berube BJ, Shetye G, Chettiar S, O’Malley T, Manning A, Flint L,
Awasthi D, Ioerger TR, Sacchettini J (2017) Improved phenoxyalkylbenzimidazoles with
activity against Mycobacterium tuberculosis appear to target QcrB. ACS Infect Dis 3:898–
916
73. McKinney JD, Zu Bentrup KH, Muñoz-Elías EJ, Miczak A, Chen B, Chan W-T,
Swenson D, Sacchettini JC, Jacobs WR Jr, Russell DG (2000) Persistence of Mycobacterium
tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase.
Nature 406:735–738
74. Muñoz-Elías EJ, McKinney JD (2005) Mycobacterium tuberculosis isocitrate lyases 1 and 2
are jointly required for in vivo growth and virulence. Nat Med 11:638–644
75. Huang H-L, Krieger IV, Parai MK, Gawandi VB, Sacchettini JC (2016) Mycobacterium
tuberculosis malate synthase structures with fragments reveal a portal for substrate/product
exchange. J Biol Chem 27421–27432
76. Krieger IV, Freundlich JS, Gawandi VB, Roberts JP, Gawandi VB, Sun Q, Owen JL,
Fraile MT, Huss SI, Lavandera J-L (2012) Structure-guided discovery of phenyl-diketo acids
as potent inhibitors of M. tuberculosis malate synthase. Chem Biol 19:1556–1567
77. Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs J-M, Winkler H, Van Gestel J,
Timmerman P, Zhu M, Lee E (2005) A diarylquinoline drug active on the ATP synthase of
Mycobacterium tuberculosis. Science 307:223–227
78. Kundu S, Biukovic G, Grüber G, Dick T (2016) Bedaquiline targets the subunit of
mycobacterial F-ATP synthase. Antimicrob Agents Chemother 6977–6979
79. Pethe K, Bifani P, Jang J, Kang S, Park S, Ahn S, Jiricek J, Jung J, Jeon HK, Cechetto J
(2013) Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat
Med 19:1157–1160
80. Bryk R, Arango N, Venugopal A, Warren JD, Park Y-H, Patel MS, Lima CD, Nathan C
(2010) Triazaspirodimethoxybenzoyls as selective inhibitors of mycobacterial lipoamide
dehydrogenase. Biochemistry 49:1616–1627
81. Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C (2011)
Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member
of three multienzyme complexes. Cell Host Microbe 9:21–31
82. Tullius MV, Harth G, Horwitz MA (2003) Glutamine synthetase GlnA1 is essential for
growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs.
Infect Immun 71:3927–3936
Impact of Target-Based Drug Design in Anti-bacterial …
341