A whole-cell phenotypic screening platform for identifying methylerythritol phosphate pathway-selective inhibitors as novel antibacterial agents

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 9, 2012, Pages 4906-4913

  Testa, Charles A ^a   Johnson, L Jeffrey ^a  

^a ECHELON BIOSCIENCES INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 KETOCLOMAZONE; ANTIINFECTIVE AGENT; DIMETHYLALLYLTRANSFERASE; FOSMIDOMYCIN; ISOPENTENYL DIPHOSPHATE; ISOPRENOID; METHYLERYTHRITOL PHOSPHATE; MEVALONIC ACID; PHOSPHATE; UNCLASSIFIED DRUG;

ARTICLE; BACTERIAL GROWTH; CELL GROWTH; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; DRUG IDENTIFICATION; ENZYME ENGINEERING; ENZYME SYNTHESIS; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; GROWTH INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; INTRACELLULAR KILLING; NONHUMAN; OPTICAL DENSITY; PHENOTYPE; PRIORITY JOURNAL; SALMONELLA ENTERICA; SALMONELLA TYPHIMURIUM; WHOLE CELL;

ANTI-BACTERIAL AGENTS; BIOSYNTHETIC PATHWAYS; CELL MEMBRANE PERMEABILITY; FOSFOMYCIN; HEMITERPENES; HIGH-THROUGHPUT SCREENING ASSAYS; METABOLIC ENGINEERING; MICROBIAL SENSITIVITY TESTS; ORGANOPHOSPHORUS COMPOUNDS; SALMONELLA TYPHIMURIUM; TERPENES;

EID: 84865421796     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00987-12     Document Type: Article

References (48)

1. Agranoff BW, Eggerer H, Henning U, Lynen F. 1960. Biosynthesis of terpenes. VII. Isopentenyl pyrophosphate isomerase. J. Biol. Chem. 235:326-332.
2. Altincicek B, et al. 2002. LytB protein catalyzes the terminal step of the 2-C-methyl-D-erythritol-4-phosphate pathway of isoprenoid biosynthesis. FEBS Lett. 532:437-440. doi:10.1016/S0014-5793(02)03726-2. (Pubitemid 35441389)
3. Amdur BH, Rilling H, Bloch K. 1957. The enzymatic conversion of mevalonic acid to squalene. J. Am. Chem. Soc. 79:2646-2647.
4. Arigoni D, et al. 1997. Terpenoid biosynthesis from 1-deoxy-D-xylulose in higher plants by intramolecular skeletal rearrangement. Proc. Natl. Acad. Sci. U. S. A. 94:10600-10605. (Pubitemid 27430780)
5. Bloch K, Chaykin S, Phillips AH, de Waard A. 1959. Mevalonic acid pyrophosphate and isopentenyl pyrophosphate. J. Biol. Chem. 234:2595-2604.
6. Bochar DA, Freisen JA, Stauffacher CV, Rodwell VW. 1999. Biosynthesis of mevalonic acid from acetyl-CoA, p 15-44. In Cane D (ed), Comprehensive natural products chemistry. Pergamon Press, Oxford, United Kingdom.
7. Boucher HW, et al. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12.
8. Brown AC, Eberl M, Crick DC, Jomaa H, Parish T. 2010. The nonmevalonate pathway of isoprenoid biosynthesis in Mycobacterium tuberculosis is essential and transcriptionally regulated by Dxs. J. Bacteriol. 192:2424-2433. doi:10.1128/JB.01402-09.
9. DeVito JA, et al. 2002. An array of target-specific screening strains for antibacterial discovery. Nat. Biotechnol. 20:478-483. doi:10.1038/nbt0502-478. (Pubitemid 34495934)
10. Dhe-Paganon S, Magrath J, Abeles RH. 1994. Mechanism of mevalonate pyrophosphate decarboxylase: evidence for a carbocationic transition state. Biochemistry 33:13355-13362. doi:10.1021/bi00249a023. (Pubitemid 24373251)
11. Duvold T, Cali P, Bravo JM, Rohmer M. 1997. Incorporation of 2-C-methyl-D-erythritol, a putative isoprenoid intermediate in the mevalonate-independent pathway, into ubiquinone and menaquinone of Escherichia coli. Tetrahedron Lett. 38:4769-4772. doi:10.1016/S0040-4039(97)01045-9.
12. ElNaggar SP, Creekmore RW, Schocken MJ, Rosen RT, Robinson RA. 1992. Metabolism of clomazone herbicide in soybean. J. Agric. Food Chem. 40:880-883. doi:10.1021/jf00017a036.
13. Eoh H, Brennan PJ, Crick DC. 2009. The Mycobacterium tuberculosis MEP (2C-methyl-D-erythritol 4-phosphate) pathway as a new drug target. Tuberculosis (Edinb.) 89:1-11.
14. Estévez JM, Cantero A, Reindl A, Reichler S, Leon P. 2001. 1-Deoxy-D-xylulose-5-phosphate synthase, a limiting enzyme for plastidic isoprenoid biosynthesis in plants. J. Biol. Chem. 276:22901-22909.
15. Ferhatoglu Y, Barrett M. 2006. Studies of clomazone mode of action. Pesticide Biochem. Physiol. 85:7-14.
16. Hahn FM, et al. 2001. 1-Deoxy-D-xylulose 5-phosphate synthase, the gene product of open reading frame (ORF) 2816 and ORF 2895 in Rhodobacter capsulatus. J. Bacteriol. 183:1-11. doi:10.1128/JB.183.1.1-11.2001. (Pubitemid 32003102)
17. Harker M, Bramley PM. 1999. Expression of prokaryotic 1-deoxy-D-xylulose-5-phosphatases in Escherichia coli increases carotenoid and ubiquinone biosynthesis. FEBS Lett. 448:115-119. doi:10.1016/S0014-5793(99) 00360-9. (Pubitemid 29151641)
18. Herz S, et al. 2000. Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate to 2-C-methyl-D- erythritol 2,4-cyclodiphosphate. Proc. Natl. Acad. Sci. U. S. A. 97:2486-2490. (Pubitemid 30159197)
19. Jomaa H, et al. 1999. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285:1573-1576. doi:10.1126/science.285.5433.1573. (Pubitemid 29420582)
20. Koppisch AT, Fox DT, Blagg BS, Poulter CD. 2002. E. coli MEP synthase: steady-state kinetic analysis and substrate binding. Biochemistry 41:236-243. doi:10.1021/bi0118207. (Pubitemid 34049399)
21. Kuzuyama T, Shimizu T, Takahashi S, Seto H. 1998. Fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway for terpenoid biosynthesis. Tetrahedron Lett. 39:7913-7916. doi:10.1016/S0040-4039(98)01755-9. (Pubitemid 28475040)
22. Kuzuyama T, Takahashi S, Watanabe H, Seto H. 1998. Direct formation of 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate from 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a new enzyme in the non-mevalonate pathway to isopentenyl diphosphate. Tetrahedron Lett. 39:4509-4512. doi:10.1016/S0040-4039(98)00802-8. (Pubitemid 28255269)
23. Kuzuyama T, Takagi M, Takahashi S, Seto H. 2000. Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis. J. Bacteriol. 182:891-897. doi:10.1128/JB.182.4.891-897.2000. (Pubitemid 30075008)
24. Lell B, et al. 2003. Fosmidomycin, a novel chemotherapeutic agent for malaria. Antimicrob. Agents Chemother. 47:735-738. doi:10.1128/AAC.47.2.735-738. 2003. (Pubitemid 36158108)
25. Lois LM, et al. 1998. Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 95:2105-2110.
26. Lüttgen H, et al. 2000. Biosynthesis of terpenoids: YchB protein of Escherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2-C- methyl-D-erythritol. Proc. Natl. Acad. Sci. U. S. A. 97:1062-1067. (Pubitemid 30080812)
27. Maragakis LL. 2010. Recognition and prevention of multidrug-resistant Gram-negative bacteria in the intensive care unit. Crit. Care Med. 38:S345-S351. doi:10.1097/CCM.0b013e3181e6cbc5.
28. Matsue Y, et al. 2010. The herbicide ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate synthase in the 2-C-methyl-D-erythritol 4-phosphate pathway and shows antibacterial activity against Haemophilus influenzae. J. Antibiot. (Tokyo) 63:583-588.
29. Matthews PD, Wurtzel ET. 2000. Metabolic engineering of carotenoid accumulation in Escherichia coli by modulation of the isoprenoid precursor pool with expression of deoxyxylulose phosphate synthase. Appl. Microbiol. Biotechnol. 53:396-400. (Pubitemid 30236111)
30. Miziorko HM, Lane MD. 1977. 3-Hydroxy-3-methylgutaryl-CoA synthase. Participation of acetyl-S-enzyme and enzyme-S-hydroxymethylgutaryl-SCoA intermediates in the reaction. J. Biol. Chem. 252:1414-1420. (Pubitemid 8047748)
31. Mueller C, Schwender J, Zeidler J, Lichtenthaler HK. 2000. Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid biosynthesis. Biochem. Soc. Trans. 28:792-793. (Pubitemid 32163270)
32. NCCLS/CLSI. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard - 6th ed. NCCLS document M7-A6. NCCLS/CLSI, Wayne, PA.
33. Putra SR, Lois LM, Campos N, Boronat A, Rohmer M. 1998. Incorporation of [2,3-13C2]- and [2,4-13C2]-D-1-deoxyxylulose into ubiquinone of Escherichia coli via the mevalonate-independent pathway for isoprenoid biosynthesis. Tetrahedron Lett. 39:23-26. doi:10.1016/S0040-4039(97)10458-0. (Pubitemid 28023440)
34. Rohdich F, et al. 2003. The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein. Proc. Natl. Acad. Sci. U. S. A. 100:1586-1591. (Pubitemid 36254491)
35. Rohdich F, et al. 1999. Cytidine 5′-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. Proc. Natl. Acad. Sci. U. S. A. 96:11758-11763.
36. Sagner S, Latzel C, Eisenreich W, Bacher A, Zenk MH. 1998. Differential incorporation of 1-deoxy-D-xylulose into monoterpenes and carotenoids in higher plants. Chem. Commun. (Camb.) 2:221-222. (Pubitemid 128675191)
37. Sambrook J, Fritsch EF, Maniatis T. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
38. Schwender J, et al. 1997. Incorporation of 1-deoxy-D-xylulose into isoprene and phytol by higher plants and algae. FEBS Lett. 414:129-134. doi:10.1016/S0014-5793(97)01002-8. (Pubitemid 27380369)
39. Siegel RE. 2008. Emerging gram-negative antibiotic resistance: daunting challenges, declining sensitivities, and dire consequences. Respir. Care 53:471-479.
40. Sprenger GA, et al. 1997. Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol. Proc. Natl. Acad. Sci. U. S. A. 94:12857-12862. (Pubitemid 27518441)
41. Testa CA, Cornish RM, Poulter CD. 2004. The sorbitol phosphotransferase system is responsible for transport of 2-C-methyl-D-erythritol into Salmonella enterica serovar Typhimurium. J. Bacteriol. 186:473-480. doi:10.1128/JB.186.2. 473-480.2004. (Pubitemid 38076438)
42. Testa CA, Brown MJ. 2003. The methylerythritol phosphate pathway and its significance as a novel drug target. Curr. Pharm. Biotechnol. 4:248-259. (Pubitemid 36958335)
43. Walsh C. 2003. Where will new antibiotics come from? Nat. Rev. Microbiol. 1:65-70.
44. Wungsintaweekul J, et al. 2001. Phosphorylation of 1-deoxy-D-xylulose by D-xylulokinase of Escherichia coli. Eur. J. Biochem. 268:310-316. (Pubitemid 32862661)
45. Xiang S, Usunow G, Lange G, Busch M, Tong L. 2007. Crystal structure of 1-deoxy-D-xylulose 5-phosphate synthase, a crucial enzyme for isoprenoids biosynthesis. J. Biol. Chem. 282:2676-2682. (Pubitemid 47076757)
46. Yong D, et al. 2009. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 53:5046-5054. doi:10.1128/AAC.00774-09.
47. Yoon SH, et al. 2005. Production of vanillin by metabolically engineered Escherichia coli. Biotechnol. Lett. 27:1829-1832.
48. Zhang B, et al. 2011. A second target of the antimalarial and antibacterial agent fosmidomycin revealed by cellular metabolic profiling. Biochemistry 50:3570-3577. doi:10.1021/bi200113y.