Strategies for potentiation of ethionamide and folate antagonists against Mycobacterium tuberculosis

Expert Review of Anti-Infective Therapy

Volumn 10, Issue 9, 2012, Pages 971-981

  Wolff, Kerstin A ^a   Nguyen, Liem ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

antifolates; ethionamide; mycobacterium; potentiation; targeting resistance; tuberculosis

Indexed keywords

2 PHENYLETHYLBUTYRATE; AMINOSALICYLIC ACID; BDM 14500; BDM 31343; BDM 31381; BDM 41906; BUTYRIC ACID DERIVATIVE; COTRIMOXAZOLE; DAPSONE; ETHIONAMIDE; FOLIC ACID ANTAGONIST; HEXADECYLOCTANOATE; ISONIAZID; OCTANOIC ACID; OXADIAZOLE DERIVATIVE; STREPTOMYCIN; SULFAMETHOXAZOLE; SULFONAMIDE; SULFONE; TRIMETHOPRIM; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; BACTERIAL INFECTION; DRUG BIOAVAILABILITY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG TARGETING; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; GENE MUTATION; HEPATITIS; HUMAN; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATIENT COMPLIANCE; PNEUMOCOCCAL INFECTION; REVIEW; SHIGELLOSIS; STAPHYLOCOCCUS INFECTION; TRANSCRIPTION REGULATION; TUBERCULOSIS; URINARY TRACT INFECTION;

DRUG DESIGN; DRUG RESISTANCE, BACTERIAL; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; ETHIONAMIDE; FOLIC ACID ANTAGONISTS; HUMANS; MYCOBACTERIUM TUBERCULOSIS; SULFONAMIDES; TUBERCULOSIS, MULTIDRUG-RESISTANT;

EID: 84868096009     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.12.87     Document Type: Review

References (93)

1. Nguyen L, Thompson CJ. Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm. Trends Microbiol. 14(7), 304-312 (2006).
2. Nguyen L, Pieters J. Mycobacterial subversion of chemotherapeutic reagents and host defense tactics: challenges in tuberculosis drug development. Annu. Rev. Pharmacol. Toxicol. 49, 427-453 (2009).
3. Dye C. Tuberculosis 2000-2010: control, but not elimination. Int. J. Tuberculosis Lung Dis. 4(12 Suppl. 2), S146-S152 (2000).
4. Gandhi NR, Moll A, Sturm AW et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368(9547), 1575-1580 (2006).
5. Jassal M, Bishai WR. Extensively drug-resistant tuberculosis. Lancet Infect. Dis. 9(1), 19-30 (2009).
6. LoBue P. Extensively drug-resistant tuberculosis. Curr. Opin. Infect. Dis. 22(2), 167-173 (2009).
7. Andronis C, Sharma A, Virvilis V, Deftereos S, Persidis A. Literature mining, ontologies and information visualization for drug repurposing. Brief. Bioinformatics 12(4), 357-368 (2011).
8. Barr J. A short history of dapsone, or an alternative model of drug development. J. Hist. Med. Allied Sci. 66(4), 425-467 (2011).
9. Global Alliance for TB Drug Development. Handbook of antituberculosis agents. Tuberculosis 88(2), 85-170 (2008).
10. Bolten BM, DeGregorio T. From the analyst's couch. Trends in development cycles. Nat. Rev. Drug Discov. 1(5), 335-336 (2002).
11. Deftereos SN, Andronis C, Friedla EJ, Persidis A, Persidis A. Drug repurposing and adverse event prediction using high-throughput literature analysis. Wiley Interdiscip. Rev. Syst. Biol. Med. 3(3), 323-334 (2011).
12. Burns M. Management of narrow therapeutic index drugs. J. Thromb. Thrombolysis 7(2), 137-143 (1999).
13. Sood A, Panchagnula R. Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index. Int. J. Pharm. 261(1-2), 27-41 (2003).
14. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Arch. Ophthalmol. 102(4), 551-553 (1984).
15. Wolff KA, Sherman MB, Nguyen L. Potentiation of available antibiotics by targeting resistance - an emerging trend in tuberculosis drug development. In: Drug Development - A Case Study Based Insight into Modern Strategies. Rundfeldt C (Ed.). InTech, NY, USA (2011).
16. Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin. Microbiol. Rev. 23(1), 160-201 (2010).
17. Wright GD. Resisting resistance: new chemical strategies for battling superbugs. Chem. Biol. 7(6), R127-R132 (2000).
18. Wright GD, Sutherland AD. New strategies for combating multidrugresistant bacteria. Trends Mol. Med. 13(6), 260-267 (2007).
19. Brossier F, Veziris N, Truffot-Pernot C, Jarlier V, Sougakoff W. Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 55(1), 355-360 (2011).
20. DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd. Ethionamide activation and sensitivity in multidrugresistant Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 97(17), 9677-9682 (2000).
21. Frénois F, Engohang-Ndong J, Locht C, Baulard AR, Villeret V. Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis. Mol. Cell 16(2), 301-307 (2004).
22. Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother. 47(12), 3799-3805 (2003).
23. Wang F, Langley R, Gulten G et al. Mechanism of thioamide drug action against tuberculosis and leprosy. J. Exp. Med. 204(1), 73-78 (2007).
24. Vannelli TA, Dykman A, Ortiz de Montellano PR. The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase. J. Biol. Chem. 277(15), 12824-12829 (2002).
25. Vilchèze C, Av-Gay Y, Attarian R et al. Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis. Mol. Microbiol. 69(5), 1316-1329 (2008).
26. Zhang Y. The magic bullets and tuberculosis drug targets. Annu. Rev. Pharmacol. Toxicol. 45, 529-564 (2005).
27. Fraaije MW, Kamerbeek NM, Heidekamp AJ, Fortin R, Janssen DB. The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase. J. Biol. Chem. 279(5), 3354-3360 (2004).
28. Baulard AR, Betts JC, Engohang-Ndong J et al. Activation of the pro-drug ethionamide is regulated in mycobacteria. J. Biol. Chem. 275(36), 28326-28331 (2000).
29. Schaaf HS, Victor TC, Venter A et al. Ethionamide cross- and co-resistance in children with isoniazid-resistant tuberculosis. Int. J. Tuberc. Lung Dis. 13(11), 1355-1359 (2009).
30. Zhang Y, Vilcheze C, Jacobs WR Jr. Mechanisms of drug resistance in Mycobacterium tuberculosis. In: Tuberculosis and the Tubercle Bacillus. Cole ST, Eisenach K, Mcmurray D, Jacobs WR Jr (Eds). ASM Press, DC, USA, 115-140 (2005).
31. Barry CE 3rd, Slayden RA, Mdluli K. Mechanisms of isoniazid resistance in Mycobacterium tuberculosis. Drug Resist. Updat. 1(2), 128-134 (1998).
32. Francois AA, Nishida CR, de Montellano PR, Phillips IR, Shephard EA. Human flavin-containing monooxygenase 2.1 catalyzes oxygenation of the antitubercular drugs thiacetazone and ethionamide. Drug Metab. Dispos. 37(1), 178-186 (2009).
33. Flipo M, Desroses M, Lecat-Guillet N et al. Ethionamide boosters: synthesis, biological activity, and structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors. J. Med. Chem. 54(8), 2994-3010 (2011).
34. Banerjee A, Dubnau E, Quemard A et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263(5144), 227-230 (1994).
35. Vilchèze C, Weisbrod TR, Chen B et al. Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrob. Agents Chemother. 49(2), 708-720 (2005).
36. Xu X, Vilchèze C, Av-Gay Y, Gómez-Velasco A, Jacobs WR Jr. Precise null deletion mutations of the mycothiol synthesis genes reveal their role in isoniazid and ethionamide resistance in Mycobacterium smegmatis. Antimicrob. Agents Chemother. 55(7), 3133-3139 (2011).
37. Willand N, Dirié B, Carette X et al. Synthetic EthR inhibitors boost antituberculous activity of ethionamide. Nat. Med. 15(5), 537-544 (2009).
38. Dover LG, Corsino PE, Daniels IR et al. Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance. J. Mol. Biol. 340(5), 1095-1105 (2004).
39. Engohang-Ndong J, Baillat D, Aumercier M et al. EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator. Mol. Microbiol. 51(1), 175-188 (2004).
40. Weber W, Schoenmakers R, Keller B et al. A synthetic mammalian gene circuit reveals antituberculosis compounds. Proc. Natl Acad. Sci. USA 105(29), 9994-9998 (2008).
41. Frénois F, Baulard AR, Villeret V. Insights into mechanisms of induction and ligands recognition in the transcriptional repressor EthR from Mycobacterium tuberculosis. Tuberculosis (Edinb.) 86(2), 110-114 (2006).
42. Carette X, Blondiaux N, Willery E et al. Structural activation of the transcriptional repressor EthR from Mycobacterium tuberculosis by single amino acid change mimicking natural and synthetic ligands. Nucleic Acids Res. 40(7), 3018-3030 (2012).
43. Nguyen L, Pieters J. The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. Trends Cell Biol. 15(5), 269-276 (2005).
44. Grau T, Selchow P, Tigges M et al. Phenylethyl butyrate enhances the potency of second-line drugs against clinical isolates of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 56(2), 1142-1145 (2012).
45. Flipo M, Desroses M, Lecat-Guillet N et al. Ethionamide boosters. 2. Combining bioisosteric replacement and structure-based drug design to solve pharmacokinetic issues in a series of potent 1,2,4-oxadiazole EthR inhibitors. J. Med. Chem. 55(1), 68-83 (2012).
46. Blakeley RL. The Biochemistry of Folic Acid and Related Pteridines. John Wiley and Sons, Inc., NY, USA (1969).
47. Green J, Nichols B, Matthews R. Folate biosynthesis, reduction, and polyglutamylation. In: Escherichia coli and Salmonella typhimurium - Cellular and Molecular Biology. Neidhardt F, Curtiss Iii R, Ingraham J et al. (Eds). ASM Press, DC, USA, 665-673 (1996).
48. Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J. Nutr. Health Aging 6(1), 39-42 (2002).
49. Bermingham A, Derrick JP. The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery. Bioessays 24(7), 637-648 (2002).
50. Bertino JR; New York Academy of Sciences. Section of Biological and Medical Sciences. Folate Antagonists as Chemotherapeutic Agents. New York Academy of Sciences, NY, USA (1971).
51. Libecco JA, Powell KR. Trimethoprim/sulfamethoxazole: clinical update. Pediatr. Rev. 25(11), 375-380 (2004).
52. Doull JA. Sulfone therapy of leprosy. Background, early history and present status. Int. J. Lepr. 31, 143-160 (1963).
53. Proctor RA. Role of folate antagonists in the treatment of methicillin-resistant Staphylococcus aureus infection. Clin. Infect. Dis. 46(4), 584-593 (2008).
54. Gangjee A, Jain HD, Kurup S. Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part I. Anticancer. Agents Med. Chem. 7(5), 524-542 (2007).
55. Gangjee A, Jain HD, Kurup S. Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part II. Anticancer. Agents Med. Chem. 8(2), 205-231 (2008).
56. Caminero JA, Sotgiu G, Zumla A, Migliori GB. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect. Dis. 10(9), 621-629 (2010).
57. Rengarajan J, Sassetti CM, Naroditskaya V, Sloutsky A, Bloom BR, Rubin EJ. The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria. Mol. Microbiol. 53(1), 275-282 (2004).
58. Hardy LW, Finer-Moore JS, Montfort WR, Jones MO, Santi DV, Stroud RM. Atomic structure of thymidylate synthase: target for rational drug design. Science 235(4787), 448-455 (1987).
59. Kwon YK, Higgins MB, Rabinowitz JD. Antifolate-induced depletion of intracellular glycine and purines inhibits thymineless death in E. coli. ACS Chem. Biol. 5(8), 787-795 (2010).
60. Fivian-Hughes AS, Houghton J, Davis EO. Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid. Microbiology (Reading, Engl.) 158(Pt 2), 308-318 (2012).
61. Sampathkumar P, Turley S, Ulmer JE, Rhie HG, Sibley CH, Hol WG. Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution. J. Mol. Biol. 352(5), 1091-1104 (2005).
62. Koehn EM, Fleischmann T, Conrad JA et al. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458(7240), 919-923 (2009).
63. Hunter JH, Gujjar R, Pang CK, Rathod PK. Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX. PLoS ONE 3(5), e2237 (2008).
64. Mathys V, Wintjens R, Lefevre P et al. Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 53(5), 2100-2109 (2009).
65. Subba Rao G, Vijayakrishnan R, Kumar M. Structure-based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Mycobacterium tuberculosis: a computer modelling approach. Chem. Biol. Drug Des. 72(5), 444-449 (2008).
66. Argyrou A, Vetting MW, Aladegbami B, Blanchard JS. Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid. Nat. Struct. Mol. Biol. 13(5), 408-413 (2006).
67. Argyrou A, Jin L, Siconilfi-Baez L, Angeletti RH, Blanchard JS. Proteomewide profiling of isoniazid targets in Mycobacterium tuberculosis. Biochemistry 45(47), 13,947-13953 (2006).
68. Wang F, Jain P, Gulten G et al. Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid. Antimicrob. Agents Chemother. 54(9), 3776-3782 (2010).
69. Forgacs P, Wengenack NL, Hall L, Zimmerman SK, Silverman ML, Roberts GD. Tuberculosis and trimethoprimYsulfamethoxazole. Antimicrob. Agents Chemother. 53(11), 4789-4793 (2009).
70. Huang TS, Kunin CM, Yan BS, Chen YS, Lee SS, Syu W Jr. Susceptibility of Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and their combination over a 12 year period in Taiwan. J. Antimicrob. Chemother. 67(3), 633-637 (2012).
71. Ong W, Sievers A, Leslie DE. Mycobacterium tuberculosis and sulfamethoxazole susceptibility. Antimicrob. Agents Chemother. 54(6), 2748; author reply 2748; author reply 2749 (2010).
72. Young LS. Reconsidering some approved antimicrobial agents for tuberculosis. Antimicrob. Agents Chemother. 53(11), 4577-4579 (2009).
73. Li R, Sirawaraporn R, Chitnumsub P et al. Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J. Mol. Biol. 295(2), 307-323 (2000).
74. Sirawaraporn W, Sirawaraporn R, Chanpongsri A, Jacobs WR Jr, Santi DV. Purification and characterization of dihydrofolate reductase from wild-type and trimethoprim-resistant Mycobacterium smegmatis. Exp. Parasitol. 72(2), 184-190 (1991).
75. Kumar M, Vijayakrishnan R, Subba Rao G. In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis dihydrofolate reductase, a potential target for anti-TB drug discovery. Mol. Divers. 14(3), 595-604 (2010).
76. El-Hamamsy MH, Smith AW, Thompson AS, Threadgill MD. Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis. Bioorg. Med. Chem. 15(13), 4552-4576 (2007).
77. Malik R, Wigney DI, Dawson D, Martin P, Hunt GB, Love DN. Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings. J. Feline Med. Surg. 2(1), 35-48 (2000).
78. Suling WJ, Reynolds RC, Barrow EW, Wilson LN, Piper JR, Barrow WW. Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase. J. Antimicrob. Chemother. 42(6), 811-815 (1998).
79. Myllykallio H, Leduc D, Filee J, Liebl U. Life without dihydrofolate reductase FolA. Trends Microbiol. 11(5), 220-223 (2003).
80. Griffin JE, Gawronski JD, Dejesus MA, Ioerger TR, Akerley BJ, Sassetti CM. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog. 7(9), e1002251 (2011).
81. de Souza GA, Leversen NA, Målen H, Wiker HG. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. J. Proteomics 75(2), 502-510 (2011).
82. Wei JR, Krishnamoorthy V, Murphy K et al. Depletion of antibiotic targets has widely varying effects on growth. Proc. Natl Acad. Sci. USA 108(10), 4176-4181 (2011).
83. Nelson RG, Rosowsky A. Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: structureYactivity and structureYselectivity correlations. Antimicrob. Agents Chemother. 45(12), 3293-3303 (2001).
84. White EL, Ross LJ, Cunningham A, Escuyer V. Cloning, expression, and characterization of Mycobacterium tuberculosis dihydrofolate reductase. FEMS Microbiol. Lett. 232(1), 101-105 (2004).
85. Baca AM, Sirawaraporn R, Turley S, Sirawaraporn W, Hol WG. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J. Mol. Biol. 302(5), 1193-1212 (2000).
86. Kai M, Matsuoka M, Nakata N et al. Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene. FEMS Microbiol. Lett. 177(2), 231-235 (1999).
87. Date AA, Vitoria M, Granich R, Banda M, Fox MY, Gilks C. Implementation of co-trimoxazole prophylaxis and isoniazid preventive therapy for people living with HIV. Bull. World Health Organ. 88(4), 253-259 (2010).
88. WHO. Tuberculosis Fact Sheet 2011.
89. February 2011 (2010).
90. Vinetz JM. Intermittent preventive treatment for malaria in sub-Saharan African: a halfway technology or a critical intervention? Am. J. Trop. Med. Hyg. 82(5), 755-756 (2010).
91. Reynolds RC, Campbell SR, Fairchild RG et al. Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation. J. Med. Chem. 50(14), 3283-3289 (2007).
92. Suling WJ, Maddry JA. Antimycobacterial activity of 1-deaza-7,8- dihydropteridine derivatives against Mycobacterium tuberculosis and Mycobacterium avium complex in vitro. J. Antimicrob. Chemother. 47(4), 451-454 (2001).
93. Ogwang S, Nguyen HT, Sherman M et al. Bacterial conversion of folinic acid is required for antifolate resistance. J. Biol. Chem. 286(17), 15377-15390 (2011).