Targeting bacterial central metabolism for drug development

Chemistry and Biology

Volumn 21, Issue 11, 2014, Pages 1423-1432

  Murima, Paul ^a   McKinney, John D ^a   Pethe, Kevin ^b,c  

^a EPFL   (Switzerland)

^b Institute Pasteur Korea   (South Korea)

^c NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; AMINO ACID; ANTIINFECTIVE AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE; PEPTIDE HYDROLASE; VITAMIN;

BACTERIAL CENTRAL METABOLISM; BACTERIAL GROWTH; BACTERIAL METABOLISM; CARBON METABOLISM; DRUG DEVELOPMENT; DRUG TOLERANCE; HOST CELL; NONHUMAN; ONCOLOGY; PENTOSE PHOSPHATE CYCLE; REVIEW; VIRUS INFECTION; ANTIBIOTIC RESISTANCE; BACTERIUM; BIOSYNTHESIS; CHEMISTRY; DRUG EFFECTS; ENERGY METABOLISM; GLUCONEOGENESIS; METABOLISM;

BACTERIA (MICROORGANISMS);

AMINO ACIDS; ANTI-BACTERIAL AGENTS; BACTERIA; DRUG RESISTANCE, BACTERIAL; ENERGY METABOLISM; GLUCONEOGENESIS; METABOLIC NETWORKS AND PATHWAYS; NAD; PEPTIDE HYDROLASES; VITAMINS;

EID: 84911470344     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2014.08.020     Document Type: Review

References (120)

1. G.L. Abrahams, A. Kumar, S. Savvi, A.W. Hung, S. Wen, C. Abell, C.E. Barry 3rd, D.R. Sherman, H.I.M. Boshoff, and V. Mizrahi Pathway-selective sensitization of Mycobacterium tuberculosis for target-based whole-cell screening Chem. Biol. 19 2012 844 854
2. A.J. Alanis Resistance to antibiotics: are we in the post-antibiotic era? Arch. Med. Res. 36 2005 697 705
3. K.R. Allison, M.P. Brynildsen, and J.J. Collins Metabolite-enabled eradication of bacterial persisters by aminoglycosides Nature 473 2011 216 220
4. D. Anastasiou, G. Poulogiannis, J.M. Asara, M.B. Boxer, J.K. Jiang, M. Shen, G. Bellinger, A.T. Sasaki, J.W. Locasale, and D.S. Auld Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses Science 334 2011 1278 1283
5. D. Anastasiou, Y. Yu, W.J. Israelsen, J.-K. Jiang, M.B. Boxer, B.S. Hong, W. Tempel, S. Dimov, M. Shen, and A. Jha Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis Nat. Chem. Biol. 8 2012 839 847
6. K. Andries, P. Verhasselt, J. Guillemont, H.W. Göhlmann, J.M. Neefs, H. Winkler, J. Van Gestel, P. Timmerman, M. Zhu, and E. Lee A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis Science 307 2005 223 227
7. D.P. Baccanari, and L.F. Kuyper Basis of selectivity of antibacterial diaminopyrimidines J. Chemother. 5 1993 393 399
8. S.-H. Baek, A.H. Li, and C.M. Sassetti Metabolic regulation of mycobacterial growth and antibiotic sensitivity PLoS Biol. 9 2011 e1001065
9. N.Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler Bacterial persistence as a phenotypic switch Science 305 2004 1622 1625
10. Barry, C.E., Boshoff, H.I., Dartois, V., Dick, T., Ehrt, S., Flynn, J., Schnappinger, D., Wilkinson, R.J., and Young, D. (2009). The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. 1-11.
11. B.D. Bax, P.F. Chan, D.S. Eggleston, A. Fosberry, D.R. Gentry, F. Gorrec, I. Giordano, M.M. Hann, A. Hennessy, and M. Hibbs Type IIA topoisomerase inhibition by a new class of antibacterial agents Nature 466 2010 935 940
12. D. Becker, M. Selbach, C. Rollenhagen, M. Ballmaier, T.F. Meyer, M. Mann, and D. Bumann Robust Salmonella metabolism limits possibilities for new antimicrobials Nature 440 2006 303 307
13. B.D. Bennett, E.H. Kimball, M. Gao, R. Osterhout, S.J. Van Dien, and J.D. Rabinowitz Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli Nat. Chem. Biol. 5 2009 593 599
14. D.J.V. Beste, K. Nöh, S. Niedenführ, T.A. Mendum, N.D. Hawkins, J.L. Ward, M.H. Beale, W. Wiechert, and J. McFadden 13C-flux spectral analysis of host-pathogen metabolism reveals a mixed diet for intracellular Mycobacterium tuberculosis Chem. Biol. 20 2013 1012 1021
15. K. Bhullar, N. Waglechner, A. Pawlowski, K. Koteva, E.D. Banks, M.D. Johnston, H.A. Barton, and G.D. Wright Antibiotic resistance is prevalent in an isolated cave microbiome PLoS ONE 7 2012 e34953
16. B. Birdsall, G.C. Roberts, J. Feeney, J.G. Dann, and A.S. Burgen Trimethoprim binding to bacterial and mammalian dihydrofolate reductase: a comparison by proton and carbon-13 nuclear magnetic resonance Biochemistry 22 1983 5597 5604
17. A. Blumenthal, C. Trujillo, S. Ehrt, and D. Schnappinger Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo PLoS ONE 5 2010 e15667
18. H.W. Boucher, G.H. Talbot, J.S. Bradley, J.E. Edwards, D. Gilbert, L.B. Rice, M. Scheld, B. Spellberg, and J. Bartlett Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America Clin. Infect. Dis. 48 2009 1 12
19. S. Brinster, G. Lamberet, B. Staels, P. Trieu-Cuot, A. Gruss, and C. Poyart Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens Nature 458 2009 83 86
20. P. Brodin, Y. Poquet, F. Levillain, I. Peguillet, G. Larrouy-Maumus, M. Gilleron, F. Ewann, T. Christophe, D. Fenistein, and J. Jang High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling PLoS Pathog. 6 2010 e1001100
21. S.A. Brown, K.L. Palmer, and M. Whiteley Revisiting the host as a growth medium Nat. Rev. Microbiol. 6 2008 657 666
22. M.P. Brynildsen, J.A. Winkler, C.S. Spina, I.C. MacDonald, and J.J. Collins Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production Nat. Biotechnol. 31 2013 160 165
23. S.R. Bushby, and G.H. Hitchings Trimethoprim, a sulphonamide potentiator Br. Pharmacol. Chemother. 33 1968 72 90
24. C.M. Cabello, W.B. Bair 3rd, and G.T. Wondrak Experimental therapeutics: targeting the redox Achilles heel of cancer Curr. Opin. Investig. Drugs 8 2007 1022 1037
25. S. Chakraborty, T. Gruber, C.E. Barry, H.I. Boshoff, and K.Y. Rhee Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in Mycobacterium tuberculosis Science 339 2013 88 91
26. H.R. Christofk, M.G. Vander Heiden, M.H. Harris, A. Ramanathan, R.E. Gerszten, R. Wei, M.D. Fleming, S.L. Schreiber, and L.C. Cantley The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth Nature 452 2008 230 233
27. B.P. Conlon, E.S. Nakayasu, L.E. Fleck, M.D. LaFleur, V.M. Isabella, K. Coleman, S.N. Leonard, R.D. Smith, J.N. Adkins, and K. Lewis Activated ClpP kills persisters and eradicates a chronic biofilm infection Nature 503 2013 365 370
28. R.A. Copeland, D.L. Pompliano, and T.D. Meek Drug-target residence time and its implications for lead optimization Nat. Rev. Drug Discov. 5 2006 730 739
29. B.D. Corbin, E.H. Seeley, A. Raab, J. Feldmann, M.R. Miller, V.J. Torres, K.L. Anderson, B.M. Dattilo, P.M. Dunman, and R. Gerads Metal chelation and inhibition of bacterial growth in tissue abscesses Science 319 2008 962 965
30. V.M. D'Costa, K.M. McGrann, D.W. Hughes, and G.D. Wright Sampling the antibiotic resistome Science 311 2006 374 377
31. V.M. D'Costa, C.E. King, L. Kalan, M. Morar, W.W.L. Sung, C. Schwarz, D. Froese, G. Zazula, F. Calmels, and R. Debruyne Antibiotic resistance is ancient Nature 477 2011 457 461
32. J.A. DeVito, J.A. Mills, V.G. Liu, A. Agarwal, C.F. Sizemore, Z. Yao, D.M. Stoughton, M.G. Cappiello, M.D.F.S. Barbosa, L.A. Foster, and D.L. Pompliano An array of target-specific screening strains for antibacterial discovery Nat. Biotechnol. 20 2002 478 483
33. J. Dhillon, K. Andries, P.P.J. Phillips, and D.A. Mitchison Bactericidal activity of the diarylquinoline TMC207 against Mycobacterium tuberculosis outside and within cells Tuberculosis (Edinb.) 90 2010 301 305
34. T. Dick, U. Manjunatha, B. Kappes, and M. Gengenbacher Vitamin B6 biosynthesis is essential for survival and virulence of Mycobacterium tuberculosis Mol. Microbiol. 78 2010 980 988
35. G. Domagk Chemotherapie der bakteriellen infektionen Angew. Chem. 48 1935 657 667
36. B.P. Duckworth, T.W. Geders, D. Tiwari, H.I. Boshoff, P.A. Sibbald, C.E. Barry 3rd, D. Schnappinger, B.C. Finzel, and C.C. Aldrich Bisubstrate adenylation inhibitors of biotin protein ligase from Mycobacterium tuberculosis Chem. Biol. 18 2011 1432 1441
37. W. Eisenreich, T. Dandekar, J. Heesemann, and W. Goebel Carbon metabolism of intracellular bacterial pathogens and possible links to virulence Nat. Rev. Microbiol. 8 2010 401 412
38. K.C. Fahnoe, M.E. Flanagan, G. Gibson, V. Shanmugasundaram, Y. Che, and A.P. Tomaras Non-traditional antibacterial screening approaches for the identification of novel inhibitors of the glyoxylate shunt in gram-negative pathogens PLoS ONE 7 2012 e51732
39. M.A. Farha, C.P. Verschoor, D. Bowdish, and E.D. Brown Collapsing the proton motive force to identify synergistic combinations against Staphylococcus aureus Chem. Biol. 20 2013 1168 1178
40. M.A. Fischbach, and C.T. Walsh Antibiotics for emerging pathogens Science 325 2009 1089 1093
41. S. Gandotra, D. Schnappinger, M. Monteleone, W. Hillen, and S. Ehrt In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice Nat. Med. 13 2007 1515 1520
42. E.D. Garber The host as a growth medium Ann. N Y Acad. Sci. 88 1960 1187 1194
43. M. Gengenbacher, S.P. Rao, K. Pethe, and T. Dick Nutrient-starved, non-replicating Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for maintenance of ATP homeostasis and viability Microbiology 156 2010 81 87
44. A. Gouzy, G. Larrouy-Maumus, T.-D. Wu, A. Peixoto, F. Levillain, G. Lugo-Villarino, J.L. Guerquin-Kern, L.P.S. de Carvalho, Y. Poquet, and O. Neyrolles Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate Nat. Chem. Biol. 9 2013 674 676
45. A. Gouzy, G. Larrouy-Maumus, D. Bottai, F. Levillain, A. Dumas, J.B. Wallach, I. Caire-Brandli, C. de Chastellier, T.-D. Wu, and R. Poincloux Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection PLoS Pathog. 10 2014 e1003928
46. S.S. Grant, B.B. Kaufmann, N.S. Chand, N. Haseley, and D.T. Hung Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals Proc. Natl. Acad. Sci. USA 109 2012 12147 12152
47. A.C. Haagsma, R. Abdillahi-Ibrahim, M.J. Wagner, K. Krab, K. Vergauwen, J. Guillemont, K. Andries, H. Lill, A. Koul, and D. Bald Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue Antimicrob. Agents Chemother. 53 2009 1290 1292
48. S. Hasan, S. Daugelat, P.S.S. Rao, and M. Schreiber Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis PLoS Comput. Biol. 2 2006 e61
49. S. Hawser, S. Lociuro, and K. Islam Dihydrofolate reductase inhibitors as antibacterial agents Biochem. Pharmacol. 71 2006 941 948
50. M. Heinemann, and U. Sauer Systems biology of microbial metabolism Curr. Opin. Microbiol. 13 2010 337 343
51. G.H. Hitchings, and J.J. Burchall Advances in Enzymology and Related Areas of Molecular Biology 2006 John Wiley & Sons Hoboken
52. A.L. Hopkins, and C.R. Groom The druggable genome Nat. Rev. Drug Discov. 1 2002 727 730
53. A.L. Hopkins, and C.R. Groom Target analysis: a priori assessment of druggability Ernst Schering Res. Found. Workshop 2003 2003 11 17
54. D.L. Johnson, C.B. Stone, D.C. Bulir, B.K. Coombes, and J.B. Mahony A novel inhibitor of Chlamydophila pneumoniae protein kinase D (PknD) inhibits phosphorylation of CdsD and suppresses bacterial replication BMC Microbiol. 9 2009 218
55. J.-S. Kim, P. Heo, T.-J. Yang, K.-S. Lee, D.-H. Cho, B.T. Kim, J.-H. Suh, H.-J. Lim, D. Shin, and S.-K. Kim Selective killing of bacterial persisters by a single chemical compound without affecting normal antibiotic-sensitive cells Antimicrob. Agents Chemother. 55 2011 5380 5383
56. J.-H. Kim, K.M. O'Brien, R. Sharma, H.I.M. Boshoff, G. Rehren, S. Chakraborty, J.B. Wallach, M. Monteleone, D.J. Wilson, and C.C. Aldrich A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence Proc. Natl. Acad. Sci. USA 110 2013 19095 19100
57. A. Koul, N. Dendouga, K. Vergauwen, B. Molenberghs, L. Vranckx, R. Willebrords, Z. Ristic, H. Lill, I. Dorange, and J. Guillemont Diarylquinolines target subunit c of mycobacterial ATP synthase Nat. Chem. Biol. 3 2007 323 324
58. A. Koul, L. Vranckx, N. Dhar, H.W.H. Göhlmann, E. Özdemir, J.-M. Neefs, M. Schulz, P. Lu, E. Mørtz, and J.D. McKinney Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism Nat. Commun. 5 2014 3369
59. Y.K. Kwon, M.B. Higgins, and J.D. Rabinowitz Antifolate-induced depletion of intracellular glycine and purines inhibits thymineless death in E. coli ACS Chem. Biol. 5 2010 787 795
60. E.-J. Lee, M.H. Pontes, and E.A. Groisman A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1Fo ATP synthase Cell 154 2013 146 156
61. X. Liu, B. Gao, V. Novik, and J.E. Galán Quantitative proteomics of intracellular Campylobacter jejuni reveals metabolic reprogramming PLoS Pathog. 8 2012 e1002562
62. L.J. Lombardo, F.Y. Lee, P. Chen, D. Norris, J.C. Barrish, K. Behnia, S. Castaneda, L.A.M. Cornelius, J. Das, and A.M. Doweyko Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays J. Med. Chem. 47 2004 6658 6661
63. S. Magnet, R.C. Hartkoorn, R. Székely, J. Pató, J.A. Triccas, P. Schneider, C. Szántai-Kis, L. Orfi, M. Chambon, and D. Banfi Leads for antitubercular compounds from kinase inhibitor library screens Tuberculosis (Edinb.) 90 2010 354 360
64. P.A. Mak, S.P.S. Rao, M. Ping Tan, X. Lin, J. Chyba, J. Tay, S.H. Ng, B.H. Tan, J. Cherian, and J. Duraiswamy A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis ACS Chem. Biol. 7 2012 1190 1197
65. V. Makarov, G. Manina, K. Mikusova, U. Möllmann, O. Ryabova, B. Saint-Joanis, N. Dhar, M.R. Pasca, S. Buroni, and A.P. Lucarelli Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis Science 324 2009 801 804
66. J. Marrero, K.Y. Rhee, D. Schnappinger, K. Pethe, and S. Ehrt Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection Proc. Natl. Acad. Sci. USA 107 2010 9819 9824
67. S. Mazurek Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells Int. J. Biochem. Cell Biol. 43 2011 969 980
68. J.D. McKinney, K. Höner zu Bentrup, E.J. Muñoz-Elías, A. Miczak, B. Chen, W.T. Chan, D. Swenson, J.C. Sacchettini, W.R. Jacobs Jr., and D.G. Russell Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase Nature 406 2000 735 738
69. J.R. Miller, S. Dunham, I. Mochalkin, C. Banotai, M. Bowman, S. Buist, B. Dunkle, D. Hanna, H.J. Harwood, and M.D. Huband A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore Proc. Natl. Acad. Sci. USA 106 2009 1737 1742
70. J. Munger, S.U. Bajad, H.A. Coller, T. Shenk, and J.D. Rabinowitz Dynamics of the cellular metabolome during human cytomegalovirus infection PLoS Pathog. 2 2006 e132
71. J. Munger, B.D. Bennett, A. Parikh, X.-J. Feng, J. McArdle, H.A. Rabitz, T. Shenk, and J.D. Rabinowitz Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy Nat. Biotechnol. 26 2008 1179 1186
72. E.J. Muñoz-Elías, and J.D. McKinney Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence Nat. Med. 11 2005 638 644
73. E.J. Muñoz-Elías, and J.D. McKinney Carbon metabolism of intracellular bacteria Cell. Microbiol. 8 2006 10 22
74. L. Pasteur La theorie des germes C. R. Assoc. Sci. 86 1878 1037 1043
75. G.J. Patti, O. Yanes, L.P. Shriver, J.-P. Courade, R. Tautenhahn, M. Manchester, and G. Siuzdak Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin Nat. Chem. Biol. 8 2012 232 234
76. D.J. Payne, M.N. Gwynn, D.J. Holmes, and D.L. Pompliano Drugs for bad bugs: confronting the challenges of antibacterial discovery Nat. Rev. Drug Discov. 6 2007 29 40
77. H. Pelicano, D. Carney, and P. Huang ROS stress in cancer cells and therapeutic implications Drug Resist. Updat. 7 2004 97 110
78. K. Pethe, P.C. Sequeira, S. Agarwalla, K. Rhee, K. Kuhen, W.Y. Phong, V. Patel, D. Beer, J.R. Walker, and J. Duraiswamy A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy Nat. Commun. 1 2010 57
79. K. Pethe, P. Bifani, J. Jang, S. Kang, S. Park, S. Ahn, J. Jiricek, J. Jung, H.K. Jeon, and J. Cechetto Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis Nat. Med. 19 2013 1157 1160
80. J.W. Phillips, M.A. Goetz, S.K. Smith, D.L. Zink, J. Polishook, R. Onishi, S. Salowe, J. Wiltsie, J. Allocco, and J. Sigmund Discovery of kibdelomycin, a potent new class of bacterial type II topoisomerase inhibitor by chemical-genetic profiling in Staphylococcus aureus Chem. Biol. 18 2011 955 965
81. S. Puckett, C. Trujillo, H. Eoh, J. Marrero, J. Spencer, M. Jackson, D. Schnappinger, K. Rhee, and S. Ehrt Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis PLoS Pathog. 10 2014 e1004144
82. J.D. Rabinowitz, J.G. Purdy, L. Vastag, T. Shenk, and E. Koyuncu Metabolomics in drug target discovery Cold Spring Harb. Symp. Quant. Biol. 76 2011 235 246
83. S.P.S. Rao, S. Alonso, L. Rand, T. Dick, and K. Pethe The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis Proc. Natl. Acad. Sci. USA 105 2008 11945 11950
84. M. Raviglione XDR-TB: entering the post-antibiotic era? Int. J. Tuberc. Lung Dis. 10 2006 1185 1187
85. E.S.C. Rittershaus, S.-H. Baek, and C.M. Sassetti The normalcy of dormancy: common themes in microbial quiescence Cell Host Microbe 13 2013 643 651
86. K. Rowland Totally drug-resistant TB emerges in India Nature News 2012 10.1038/nature.2012.9797 Published January 13, 2012
87. M.I. Samanovic, C. Ding, D.J. Thiele, and K.H. Darwin Copper in microbial pathogenesis: meddling with the metal Cell Host Microbe 11 2012 106 115
88. C. Sassetti, and E.J. Rubin Genomic analyses of microbial virulence Curr. Opin. Microbiol. 5 2002 27 32
89. U.E. Schaible, and S.H. Kaufmann Iron and microbial infection Nat. Rev. Microbiol. 2 2004 946 953
90. E.K. Schmitt, M. Riwanto, V. Sambandamurthy, S. Roggo, C. Miault, C. Zwingelstein, P. Krastel, C. Noble, D. Beer, and S.P.S. Rao The natural product cyclomarin kills Mycobacterium tuberculosis by targeting the ClpC1 subunit of the caseinolytic protease Angew. Chem. Int. Ed. Engl. 50 2011 5889 5891
91. D. Schnappinger, S. Ehrt, M.I. Voskuil, Y. Liu, J.A. Mangan, I.M. Monahan, G. Dolganov, B. Efron, P.D. Butcher, C. Nathan, and G.K. Schoolnik Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment J. Exp. Med. 198 2003 693 704
92. M. Schreiber, I. Res, and A. Matter Protein kinases as antibacterial targets Curr. Opin. Cell Biol. 21 2009 325 330
93. P.T. Schumacker Reactive oxygen species in cancer cells: live by the sword, die by the sword Cancer Cell 10 2006 175 176
94. N.P. Shah, C. Tran, F.Y. Lee, P. Chen, D. Norris, and C.L. Sawyers Overriding imatinib resistance with a novel ABL kinase inhibitor Science 305 2004 399 401
95. S.A. Stanley, A.K. Barczak, M.R. Silvis, S.S. Luo, K. Sogi, M. Vokes, M.-A. Bray, A.E. Carpenter, C.B. Moore, and N. Siddiqi Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth PLoS Pathog. 10 2014 e1003946
96. F. Stavru, F. Bouillaud, A. Sartori, D. Ricquier, and P. Cossart Listeria monocytogenes transiently alters mitochondrial dynamics during infection Proc. Natl. Acad. Sci. USA 108 2011 3612 3617
97. J. Storm, S. Sethia, G.J. Blackburn, A. Chokkathukalam, D.G. Watson, R. Breitling, G.H. Coombs, and S. Müller Phosphoenolpyruvate carboxylase identified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism PLoS Pathog. 10 2014 e1003876
98. B.A. Teicher, W.M. Linehan, and L.J. Helman Targeting cancer metabolism Clin. Cancer Res. 18 2012 5537 5545
99. D.A. Tennant, R.V. Durán, and E. Gottlieb Targeting metabolic transformation for cancer therapy Nat. Rev. Cancer 10 2010 267 277
100. R. Then, and P. Angehrn Sulphonamide-induced 'thymineless death' in Escherichia coli J. Gen. Microbiol. 76 1973 255 263
101. J. Timm, F.A. Post, L.G. Bekker, G.B. Walther, H.C. Wainwright, R. Manganelli, W.T. Chan, L. Tsenova, B. Gold, and I. Smith Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients Proc. Natl. Acad. Sci. USA 100 2003 14321 14326
102. D. Trachootham, J. Alexandre, and P. Huang Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev. Drug Discov. 8 2009 579 591
103. M.V. Tullius, G. Harth, and M.A. Horwitz Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs Infect. Immun. 71 2003 3927 3936
104. A.S. van Miert The sulfonamide-diaminopyrimidine story J. Vet. Pharmacol. Ther. 17 1994 309 316
105. M.G. Vander Heiden Targeting cancer metabolism: a therapeutic window opens Nat. Rev. Drug Discov. 10 2011 671 684
106. M.G. Vander Heiden, L.C. Cantley, and C.B. Thompson Understanding the Warburg effect: the metabolic requirements of cell proliferation Science 324 2009 1029 1033
107. L. Vastag, E. Koyuncu, S.L. Grady, T.E. Shenk, and J.D. Rabinowitz Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism PLoS Pathog. 7 2011 e1002124
108. N.M. Vega, K.R. Allison, A.S. Khalil, and J.J. Collins Signaling-mediated bacterial persister formation Nature Chemical Biology 8 2012 431 433
109. Y. Wakamoto, N. Dhar, R. Chait, K. Schneider, F. Signorino-Gelo, S. Leibler, and J.D. McKinney Dynamic persistence of antibiotic-stressed mycobacteria Science 339 2013 91 95
110. A. Walburger, A. Koul, G. Ferrari, L. Nguyen, C. Prescianotto-Baschong, K. Huygen, B. Klebl, C. Thompson, G. Bacher, and J. Pieters Protein kinase G from pathogenic mycobacteria promotes survival within macrophages Science 304 2004 1800 1804
111. J. Wang, S.M. Soisson, K. Young, W. Shoop, S. Kodali, A. Galgoci, R. Painter, G. Parthasarathy, Y.S. Tang, and R. Cummings Platensimycin is a selective FabF inhibitor with potent antibiotic properties Nature 441 2006 358 361
112. P.S. Ward, and C.B. Thompson Metabolic reprogramming: a cancer hallmark even warburg did not anticipate Cancer Cell 21 2012 297 308
113. J.-R. Wei, V. Krishnamoorthy, K. Murphy, J.-H. Kim, D. Schnappinger, T. Alber, C.M. Sassetti, K.Y. Rhee, and E.J. Rubin Depletion of antibiotic targets has widely varying effects on growth Proc. Natl. Acad. Sci. USA 108 2011 4176 4181
114. S. Woong Park, M. Klotzsche, D.J. Wilson, H.I. Boshoff, H. Eoh, U. Manjunatha, A. Blumenthal, K. Rhee, C.E. Barry 3rd, and C.C. Aldrich Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression PLoS Pathog. 7 2011 e1002264
115. K. Yamada, and T. Noguchi Nutrient and hormonal regulation of pyruvate kinase gene expression Biochem. J. 337 1999 1 11
116. D. Yin, B. Fox, M.L. Lonetto, M.R. Etherton, D.J. Payne, D.J. Holmes, M. Rosenberg, and Y. Ji Identification of antimicrobial targets using a comprehensive genomic approach Pharmacogenomics 5 2004 101 113
117. L. Zhang, F. Fan, L.M. Palmer, M.A. Lonetto, C. Petit, L.L. Voelker, A. St John, B. Bankosky, M. Rosenberg, and D. McDevitt Regulated gene expression in Staphylococcus aureus for identifying conditional lethal phenotypes and antibiotic mode of action Gene 255 2000 297 305
118. Y.J. Zhang, M.C. Reddy, T.R. Ioerger, A.C. Rothchild, V. Dartois, B.M. Schuster, A. Trauner, D. Wallis, S. Galaviz, and C. Huttenhower Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing Cell 155 2013 1296 1308
119. J. Zheng, E.J. Rubin, P. Bifani, V. Mathys, V. Lim, M. Au, J. Jang, J. Nam, T. Dick, and J.R. Walker Para-aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis J. Biol. Chem. 288 2013 23447 23456
120. S. Zlitni, L.F. Ferruccio, and E.D. Brown Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation Nat. Chem. Biol. 9 2013 796 804