Inhibition of Mycoplasma pneumoniae growth by FDA-approved anticancer and antiviral nucleoside and nucleobase analogs
详细信息 查看全文
- 作者：Ren Sun (2)
Liya Wang (2) - 关键词：Mycoplasma pneumoniae ; Growth inhibition ; 6 ; thioguanine ; Trifluorothymidine ; Hypoxanthine guanine phosphoribosyl transferase ; Thymidine kinase
- 刊名：BMC Microbiology
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：13
- 期：1
- 全文大小：350KB
- 参考文献：1. Razin S, Yogev D, Naot Y: Molecular biology and pathogenicity of Mycoplasmas . / Microbiol Mol Biol Rev 1998, 62:1094-156.
2. Waites KB, Talkington DF: Mycoplasma pneumoniae and its role as a human pathogen. / Clin Microbiol Rev 2004, 17:697-28. CrossRef
3. Narita M: Pathogenesis of extrapulmonary manifestations of Mycoplasma penumoniae infection with special reference to pneumonia. / J infec Chemother 2010, 16:162-69. CrossRef
4. Lenglet A, Herrado Z, Magiorakos A, Leitmeyer K, Coulombier D: Surveillance status and recent data for Mycoplasam pneumoniae infection in the European Union and European Economic area, January 2012. / Euro Surveill 2012, 17:2-.
5. Pereyre S, Renaudin H, Charron A, Bebear C: Clonal spread of Mycoplasma pneumoniae in primary school, Bordeaux, France. / Emerg Infect Dis 2012, 18:343-45. CrossRef
6. Lung D, Chan Y, Kwong L, Que T: Severe community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae in a 6-year-old boy. / Hong Kong Med J 2011, 17:407-09.
7. Hsieh Y, Tsao K, Huang C, Tong S, Winchell J, Huang Y, Shia S, Lai S, Lin T: Life-threatening pneumonia caused by macrolide-resistant Mycoplasma pneumoniae . / Pediatr Infect Dis 2012, 31:208-09. CrossRef
8. Morozumi M, Takahashi T, Ubukata K: Macrolide-resistant Mycoplasma pneumoniae : characteristics of isolates and clinical aspects of community-acquired pneumonia. / J Infec Chemother 2010, 16:78-6. CrossRef
9. Bebear C, Pereyre S, Peuchant O: Mycoplasma pneumoniae : susceptibility and resistance to antibiotics. / Future Microbiol 2011, 6:423-31. CrossRef
10. Yamada M, Buller R, Bledsoe S, Storch G: Rising rates of macrolode-resistant Mycoplasma pneumoniae in the central United State. / Pediatr Infect Dis 2012, 31:409. CrossRef
11. Zhao F, Lv M, Tao X, Huang H, Zhang B, Zhang Z, Zhang J: Antibiotic sensitivity of 40 Mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant isolates from Beijing, China. / Antimicrob Agents Chemother 2012, 56:1108-109. CrossRef
12. Cao B, Zhao C, Yin Y, Zhao F, Song S, Bai L, Zhang J, Liu Y, Zhang Y, Wang H, Wang C: High prevalence of macrolide resistance in Mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in China. / Clin Infect Dis 2010, 51:189-94. CrossRef
13. Scozzafava A, Owa T, Mastrolorenzo A, Supuran C: Anticancer and antiviral sulfonamides. / Curr Med Chem 2003, 10:925-53. CrossRef
14. Jackman A, Calvert A: Folate-based thymidylate synthase inhibitors as anticancer drugs. / Ann Oncol 1995, 6:871-81.
15. Costi M, Tondi D, Rinaldi M, Barlocco D, Pecorari P, Soragni F, Venturelli A, Stroud R: Structure-based studies on species-specific inhibition of thymidylate synthase. / Biochim Biophys Acta 2002, 1587:206-14. CrossRef
16. Lee W, Martin J: Perspectives on the development of acyclic nucleoside analogs as antiviral drugs. / Antiviral Res 2006, 71:254-59. CrossRef
17. Arts E, Hazuda D: HIV-1 antiretroviral drug therapy. / Cold Spring Harb Perspect Med 2012, 2:1-3. CrossRef
18. Carnrot C, Vogel S, Byun Y, Wang L, Tjarks W, Eriksson S, Phipps A: Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs. / Biol Chem 2006, 387:1575-581. CrossRef
19. Srivastava R, Bhargava A, Singh R: Synthesis and antimicrobial activity of some novel nucleoside analogues of adenosine and 1,3-dideazaadenosine. / Bioorg Med Chem Lett 2007, 17:6239-244. CrossRef
20. Van Calenberg S, Pochet S, Munier-Lehmann H: Drug design and identification of potent leads against Mycobacterium tuberculosis thymidine monophosphate kinase. / Curr Top Med Chem 2012, 12:694-05. CrossRef
21. Choi J, Plummer M, Starr J, Desbonnet C, Soutter H, Chang J, Miller J, Dillman K, Miller A, Roush W: Structure guided development of novel thymidine mimetics targeting Pseudomonas aeruginosa thymidylate kinase: from hit to lead generation. / J Med Chem 2012, 55:852-70. CrossRef
22. Martinez-Botella G, Breen J, Duffy J, Dumas J, Geng B, Gowers I, Green O, Guler S, Hentemann M, Hernandez-Huan F, Joseph-McCarthy D, Kawatkar S, Larsen N, Lazari O, Loch J, Macritchie J, McKenzie A, Newman J, Olivier N, Otterson L, Owens A, Read J, Sheppard D, Keating T: Discovery of selective and potent inhibitors of gram-positive bacterial thymidylate kinase (TMK). / J Med Chem 2012, 55:10010-0021. CrossRef
23. Keating T, JV N, Olivier N, Otterson L, Andrews B, Boriack-Sjodin P, Breen J, Dolg P, Dumas J, Gangl E, Green O, Guler S, Hentemann M, Joseph-McCarthy D, Kawatkar S, Kutschke A, Loch J, McKenzie A, Pradeepan S, Prasad S, Martinez-Botella G: In vivo validation of thymidylate kinase (TMK) with a rationally designed, selective antibacterial compound. / ACS Chem Biol 2012, 7:1866-872. CrossRef
24. Mitchell A, Finch L: Pathways of nucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides . / J Bacteriol 1977, 130:1047-054.
25. Mitchell A, Sin I, Finch L: Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides . / J Bacteriol 1978, 134:706-12.
26. Mitchell A, Finch L: Enzymes of pyrimidine metabolism in Mycoplasma mycoides subsp. mycoides . / J Bacteriol 1979, 137:1073-080.
27. Pollack J, Williams M, Banzon J, Jones M, Harvey L, Tully J: Comparative metabolism of Mesoplasma, Entomoplasma, Mycoplasma , and Acholeplasma . / Int J Syst Bacteriol 1996, 46:885-90. CrossRef
28. Pollack J, Williams M, McElhaney R: The comparative metabolism of the Mollicutes ( Mycoplasmas ): the utility for taxonomic classification and the relationship of putative gene annotation and phylogeny to enzymatic function in the smallest free-living cells. / Crit Rev Microbiol 1997, 23:269-54. CrossRef
29. Wang L, Westberg J, B?lske G, Eriksson S: Novel deoxynucleoside-phosphorylating enzymes in Mycoplasmas: evidence for efficient utilization of deoxynucleosides. / Mol Microbiol 2001, 42:1065-073. CrossRef
30. Carnrot C, Wehelie R, Eriksson S, B?lske G, Wang L: Molecular characterization of thymidine kinase from Ureaplasma urealyticum : nucleoside analogues as potent inhibitors of mycoplasma growth. / Mol Microbiol 2003, 50:771-80. CrossRef
31. Wang L, Hames C, Schmidt S, Stülke J: Upregulation of thymidine kinase activity compensates for loss of thymidylate synthase activity in Mycoplasma pneumoniae . / Mol Microbiol 2010, 77:1502-511. CrossRef
32. Yus E, Maier T, Michalodimitrakis K, van Noort V, Yamada T, Chen W, Wodke J, Güell M, Martinez S, Bourgeois R, Kühner S, Raineri E, Letunic I, Kalinina O, Rode M, Herrmann R, Gutierrez-Gallego R, Russell R, Gavin A, Bork P, Serrano L: Impact of genome reduction on bacterial metabolism and its regulation. / Science 2009, 326:1263-268. CrossRef
33. Hutchison C, Peterson S, Gill S, Cline R, White O, Fraser C, Smith HO, Venter JC: Global transposon mutagenesis and a minimal Mycoplasma genome. / Science 1999, 286:2165-169. CrossRef
34. Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M, Hutchison CA, Smith HO, Venter JC: Essential genes of a minimal bacterium. / Proc Natl Acad Sci USA 2006, 103:425-30. CrossRef
35. Wehelie R, Eriksson S, B?lske G, Wang L: Growth inhibition of Mycoplasma by nucleoside analogues. / Nucleosides, Nucleotides & Nucleic Acid 2004, 23:1499-502. CrossRef
36. Egeblad L, Welin M, Flodin S, Gr?slund S, Wang L, Balzarini J, Eriksson S, Nordlund P: Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism. / PLoS One 2012, 7:e37724. CrossRef
37. Hindorf U, Lindqvist M, Peterson C, S?derkvist P, Str?m M, Hjortswang H, Pousette A, Almer S: Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. / Gut 2006, 55:1423-431. CrossRef
38. Santi D, Sakai T: Thymidylate synthetase. Model studies of inhibition by 5-trifluoromethyl-2'-deoxyuridylic acid. / Biochemistry 1971, 10:3598-607. CrossRef
39. Welin M, Kosinska U, Mikkelsen N, Carnrot C, Zhu C, Wang L, Eriksson S, Munch-Petersen B, Eklund H: Structures of thymidine kinase 1 of human and mycoplasmic origin. / Proc Natl Acad Sci USA 2004, 101:17970-7975. CrossRef
40. Wang L, Munch-Petersen B, Herrstr?m Sj?berg A, Hellman U, Bergman T, J?rnvall H, Eriksson S: Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates. / FEBS Lett 1999, 443:170-74. CrossRef
41. Wang J, Su C, Neuhard J, Eriksson S: Expression of human mitochondrial thymidine kinase in Escherichia coli: correlation between the enzymatic activity of pyrimidine nucleoside analogues and their inhibitory effect on bacterial growth. / Biochem Pharmacol 2000, 59:1583-588. CrossRef
42. Pachkov M, Dandekar T, Korbel J, Bork P, Schuster S: Use of pathway analysis and genome context methods for functional genomics of Mycoplasma pneumoniae nucleotide metabolism. / Gene 2007, 396:215-25. CrossRef
43. Ding L, Zhang F, Liu H, Gao X, Bi H, Wang XQ, Chen B, Zhang Y, Zhao L, Zhong G, Hu P, Chen M, Huang M: Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leikopenia in the treatment of inflammatroy bowel disease. / Inflamm Bowel Dis 2012, 18:63-3. CrossRef
44. Welin M, Egeblad L, Johansson A, Stenmark P, Wang L, Flodin S, Nyman T, Trésaugues L, Kotenyova T, Johansson I, Eriksson S, Eklund H, Nordlund P: Structural and function studies of the human phosphoribosyltransferase domain containing protein 1. / FEBS J 2010, 277:4920-930. CrossRef
45. Traut T: Physiological concentrations of purines and pyrimidines. / Mol Cell Biochem 1994, 140:1-2. CrossRef
46. Cesnek M, Hockova D, Holy A, Dracinsky M, Baszczynski O, Jersey J, DT K, Guddat L: Synthesis of 9-phosphonoalkyl and 9-phosphonoalkoxyalkyl purines: evaluation of their ability to act as inhibitors of Plasmodium falciparum , Plasmodium vivax and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases. / Bioorg Med Chem 2012, 20:1076-089. CrossRef
47. Sun X, Sharling L, Muthalagi M, Mudeppa D, Pankiewicz K, Felczak K, Rathod P, Mead J, Striepen B, Hedstrom L: Prodrug activation by Cryptosporidium thymidine kinase. / J Biol Chem 2010, 285:15916-5922. CrossRef
48. Sandrini M, Shannon O, Clausen A, Bj?rck L, Piskur J: Deoxyribonucleoside kinases activate nucleoside antibiotics in severely pathogenic bacteria. / Antimicrob Agents Chemother 2007, 51:2726-732. CrossRef
49. Halbedel S, Stülke J: Dual phosphorylation of Mycoplasma pneumoniae HPr by enzyme I and HPr kinase suggests an extended phosphoryl group susceptibility of HPr. / FEMS Microbiol Lett 2004, 247:193-98. CrossRef
50. Okazaki N, Narita M, Yamada S, Izumikawa K, Umetsu M, Kenri Y, Sasaky Y, Arakawa Y, Sasaky T: Characteristics of macrolide-resistant Mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro. / Microbiol Immunol 2001, 45:617-20.
51. Sharif H, von Euler H, Westberg S, He E, Wang L, Eriksson S: A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphoma. / Vet J 2012, 194:40-7. CrossRef
52. Wang L: The role of Ureaplasma nucleoside monophosphate kinases in the synthesis of nucleoside triphosphates. / FEBS J 2007, 274:1983-990. CrossRef - 作者单位：Ren Sun (2)
Liya Wang (2)
2. Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, Box 575, SE-751 23, Uppsala, Sweden - ISSN：1471-2180
文摘
Background Mycoplasma pneumoniae (Mpn) is a human pathogen that causes acute and chronic respiratory diseases and has been linked to many extrapulmonary diseases. Due to the lack of cell wall, Mpn is resistant to antibiotics targeting cell wall synthesis such as penicillin. During the last 10 years macrolide-resistant Mpn strains have been frequently reported in Asian countries and have been spreading to Europe and the United States. Therefore, new antibiotics are needed. In this study, 30 FDA-approved anticancer or antiviral drugs were screened for inhibitory effects on Mpn growth and selected analogs were further characterized by inhibition of target enzymes and metabolism of radiolabeled substrates. Results Sixteen drugs showed varying inhibitory effects and seven showed strong inhibition of Mpn growth. The anticancer drug 6-thioguanine had a MIC (minimum inhibitory concentration required to cause 90% of growth inhibition) value of 0.20 μg ml-1, whereas trifluorothymidine, gemcitabine and dipyridamole had MIC values of approximately 2 μg ml-1. In wild type Mpn culture the presence of 6-thioguanine and dipyridamole strongly inhibited the uptake and metabolism of hypoxanthine and guanine while gemcitabine inhibited the uptake and metabolism of all nucleobases and thymidine. Trifluorothymidine and 5-fluorodeoxyuridine, however, stimulated the uptake and incorporation of radiolabeled thymidine and this stimulation was due to induction of thymidine kinase activity. Furthermore, Mpn hypoxanthine guanine phosphoribosyl transferase (HPRT) was cloned, expressed, and characterized. The 6-thioguanine, but not other purine analogs, strongly inhibited HPRT, which may in part explain the observed growth inhibition. Trifluorothymidine and 5-fluorodeoxyuridine were shown to be good substrates and inhibitors for thymidine kinase from human and Mycoplasma sources. Conclusion We have shown that several anticancer and antiviral nucleoside and nucleobase analogs are potent inhibitors of Mpn growth and that the mechanism of inhibition are most likely due to inhibition of enzymes in the nucleotide biosynthesis pathway and nucleoside transporter. Our results suggest that enzymes in Mycoplasma nucleotide biosynthesis are potential targets for future design of antibiotics against Mycoplasma infection.