FP6 banner New Medicines For Tuberculosis

List of publications directly emanating from the project


1. Chalut, C., Botella, L., de Sousa-D'Auria, C., Houssin, C. & Guilhot, C. (2006).
The non redundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria.
Proc. Natl. Acad. Sci. (USA), 103: 8511-8516.

2. Fernandez, P., Saint-Joanis, B., Barilone, N., Jackson, M., Gicquel, B, Cole, S.T., & Alzari, P.M. (2006)
The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth.
J. Bacteriol. 188: 7778 - 7784.

3. Henriksson, L. M., Björkelid, C., Mowbray, S. L., & Unge, T. (2006)
The 1.9 Å resolution structure of the Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target.
Acta Crystallographica D, D62: 807-813.

4. Johansson, P., Castell, A., Jones, T. A., & Bäckbro, K. (2006)
Structure and function of Rv0130, a conserved hypothetical protein from Mycobacterium tuberculosis
Protein Science, 15: 2300-2309.

5. McLean, K.J., Clift, D., Lewis, D.G., Sabri, M., Balding, P.R., Sutcliffe, M.J., Leys, D. & Munro, A.W. (2006).
The preponderance of P450s in the Mycobacterium tuberculosis genome.
Trends Microbiol. 14: 220-228.

6. McLean, K.J., Dunford, A.J., Sabri, M., Neeli, R., Girvan, H.M., Balding, P.R., Leys, D., Seward, H.E., Marshall, K.R. and Munro. A.W. (2006).
CYP121, CYP51 and associated redox systems in Mycobacterium tuberculosis: Towards deconvoluting enzymology of P450 systems in a human pathogen.
Biochem. Soc. Trans. 34: 1178 - 1182.

7. McLean, K.J., Warman, A.J., Seward, H.E., Marshall, K.R., Girvan, H.M., Cheesman, M.R., Waterman, M.R. & Munro, A.W. (2006).
Biophysical characterization of the sterol demethylase P450 (CYP51) from Mycobacterium tuberculosis, its cognate ferredoxin (Fdx) and their interactions.
Biochemistry 45: 8427-8443.

8. Prado, S., Ledeit, H., Michel, S., Koch, M., Darbord, J.C., Cole, S.T., Tillequin, F.; Brodin, P. (2006).
Benzofuro[3,2-f]benzopyrans: A New Class of Antitubercular Agents.
Bioorg. Med. Chem. 14: 5423-5428.

9. Saint-Joanis, B., Demangel, C., Jackson, M., Brodin, P., Marsollier, L., Boshoff, H., & Cole, S.T. ( 2006)
Inactivation of Rv2525c, a Substrate of the Twin Arginine Translocation (Tat) System of Mycobacterium tuberculosis, Increases β-Lactam Susceptibility and Virulence
J. Bacteriol. 188: 6669-6679.

10. Seward, H.E., Roujeinikova, A., McLean, K.J., Munro, A.W. & Leys, D. (2006).
Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole complex reveals new azole drug-P450 binding mode.
J. Biol. Chem. 281: 39437 - 39443.


11. Bellinzoni, M., Wehenkel, A., Shepard, W. & Alzari, P.M. (2007)
Insights into the catalytic mechanism of PPM Ser/Thr phosphatases from the atomic resolution structures of a mycobacterial enzyme.
Structure, in press.

12. Brosch, R. & Vincent, V. (2007)
Cutting-edge science and the future of tuberculosis control.
Bulletin of the World Health Organization 85: 410-412.

13. de Jonge, M.I., Pehau-Arnaudet, G., Fretz, M.M., Romain, F., Bottai, D., Brodin, P., Honoré N., Marchal, G., Jiskoot, W., England, P., Cole, S.T., & Brosch, R. (2007)
ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity.
J. Bacteriol. 189: 6028-6034.

14. Dunford, A.J., McLean, K.J., Sabri, M., Seward, H.E., Heyes, D.J., Scrutton, N.S. & Munro, A.W. (2007).
Rapid P450 heme iron reduction by laser photoexcitation of Mycobacterium tuberculosis CYP121 and CYP51B1: Analysis of CO complexation reactions and reversibility of the P450/P420 equilibrium.
J. Biol. Chem. (submitted).

15. Guerin, M.E., Kordulakova, J., Schaeffer, F., Svetlikova, Z., Buschiazzo, A., Giganti, D., Gicquel, B., Mikusova, K., Jackson M. and Alzari, P.M. (2007)
Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.
J. Biol. Chem, May 16 in press. PMID: 17510062

16. Henriksson, L.M., Unge, T., Carlsson, J., Åqvist, J., Mowbray, S.L. & Jones, T.A. (2007)
Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase provide new insights into catalysis.
J. Biol. Chem. 282 19905-19916.

17. Janin, Y.L. (2007)
Antituberculosis drugs: Ten years of research.
Bioorganic & Medicinal Chemistry. In press.

18. Lucarelli, D., Russo, S., Garman, E., Milano, A., Meyer-Klaucke, W., & Pohl, E. (2007)
Crystal Structure and Function of the Zinc Uptake Regulator FurB from Mycobacterium tuberculosis.
J. Biol. Chem. 282: 9914 - 9922.

19. Maciag, A., Dainese, E., Rodriguez, E.G., Milano, A., Provvedi, R., Pasca, M.R., Smith, I., Palù, G., Riccardi,G., and Manganelli, R. (2007)
Global analysis of Mycobacterium tuberculosis Zur (FurB) regulon.
J. Bacteriol. 189: 730 - 740.

20. McLean, K.J., Dunford, A.J., Neeli, R., Driscoll, M.D and Munro, A.W. (2007).
Structure, function and drug targeting in Mycobacterium tuberculosis cytochrome P450 systems.
Arch. Biochem. Biophys. (in press).

21. Munro, A.W., Girvan, H.M. and McLean, K.J. (2007).
Cytochrome P450-redox partner fusion enzymes.
Biochim. Biophys. Acta 1770, 345-359.

22. Prado, S., Janin Y.L., Saint-Joanis, B., Brodin, P., Michel, S., Koch, M., Cole, S.T., Tillequin, F., & Bost, P.E. (2007)
Synthesis and antimycobacterial evaluation of benzofurobenzopyran analogues.
Bioorg Med Chem. 2007 (on line)

23. Prado, S., Toum, V., Saint-Joanis, B., Michel, S., Koch, M., Cole, S.T., Tillequin, F., & Janin Y.L., (2007)
Antimycobacterial Benzofuro[3,2-f]chromenes from a 5-Bromochromen-6-ol.
J. Synthetic Organic Chem. 10 1566 - 1570.

24. Sacco, E., Legendre, V., Laval, F., Zerbib, D., Montrozier, H., Eynard, N., Guilhot, C., Daffé, M., & Quémard, A (2007).
Rv3389C from Mycobacterium tuberculosis, a member of the (R)-specific hydratase/dehydratase family.
Biochim. Biophys. Acta- Proteins and Proteomics 1774: 303-311.

25. Sacco, E., Suarez Covarrubias, Adrian., O'Hare, H.M., Carroll, P., Eynard, N., Jones, T.A., Parish, T., Daffé, M., Bäckbro, K., & Quémard, K. (2007)
The missing piece of the type II Fatty Acid Synthase system from Mycobacterium tuberculosis.
Proc. Nat. Acad. Sci. 104: 14628-14633.


26. Alvey, L., S. Prado, V. Huteau, B. Saint-Joanis, S. Michel, M. Koch, S. T. Cole, F. Tillequin & Y. L. Janin, (2008)
A new synthetic access to furo[3,2-f]chromene analogues of an antimycobacterial.
Bioorg Med Chem 16: 8264-8272.

27. Balding, P. R., C. S. Porro, K. J. McLean, M. J. Sutcliffe, J. D. Marechal, A. W. Munro & S. P. Visser, (2008)
How Do Azoles Inhibit Cytochrome P450 Enzymes? A Density Functional Study.
J Phys Chem 112: 12911-12918.

28. Balganesh, T. S., P. M. Alzari & S. T. Cole, (2008)
Rising standards for tuberculosis drug development.
Trends Pharmacol Sci 29: 576-581.

29. Belanova, M., P. Dianiskova, P. J. Brennan, G. C. Completo, N. L. Rose, T. L. Lowary & K. Mikusova, (2008)
Galactosyl transferases in mycobacterial cell wall synthesis.
J Bacteriol 190: 1141-1145.

30. Brown, A. C. & T. Parish, (2008)
Dxr is essential in Mycobacterium tuberculosis and fosmidomycin resistance is due to a lack of uptake.
BMC Microbiol 8: 78.

31. Carroll, P., C. A. Pashley & T. Parish, (2008)
Functional analysis of GlnE, an essential adenylyl transferase in Mycobacterium tuberculosis.
J Bacteriol 190: 4894-4902.

32. Covarrubias, A. S., M. Hogbom, T. Bergfors, P. Carroll, K. Mannerstedt, S. Oscarson, T. Parish, T. A. Jones & S. L. Mowbray, (2008)
Structural, biochemical, and in vivo investigations of the threonine synthase from Mycobacterium tuberculosis.
J Mol Biol 381: 622-633.

33. England, P., A. Wehenkel, S. Martins, S. Hoos, G. Andre-Leroux, A. Villarino & P. M. Alzari, (2008)
The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling.
FEBS Lett. [Epub ahead of print]

34. Frigui, W., D. Bottai, L. Majlessi, M. Monot, E. Josselin, P. Brodin, T. Garnier, B. Gicquel, C. Martin, C. Leclerc, S. T. Cole & R. Brosch, (2008)
Control of Mtb ESAT-6 secretion and specific T cell recognition by PhoP.
PLoS Pathog 4: e33.

35. Hegymegi-Barakonyi, B., R. Szekely, Z. Varga, R. Kiss, G. Borbely, G. Nemeth, P. Banhegyi, J. Pato, Z. Greff, Z. Horvath, G. Meszaros, J. Marosfalvi, D. Eros, C. Szantai-Kis, N. Breza, S. Garavaglia, S. Perozzi, M. Rizzi, D. Hafenbradl, M. Ko, Y. Av-Gay, B. M. Klebl, L. Orfi & G. Keri, (2008)
Signalling inhibitors against Mycobacterium tuberculosis - early days of a new therapeutic concept in tuberculosis.
Curr Med Chem 15: 2760-2770.

36. Krajewski, W. W., R. Collins, L. Holmberg-Schiavone, T. A. Jones, T. Karlberg & S. L. Mowbray, (2008)
Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.
J Mol Biol 375: 217-228.

37. McLean, K. J., P. Carroll, D. G. Lewis, A. J. Dunford, H. E. Seward, R. Neeli, M. R. Cheesman, L. Marsollier, P. Douglas, W. E. Smith, I. Rosenkrands, S. T. Cole, D. Leys, T. Parish & A. W. Munro, (2008)
Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv.
J Biol Chem 283: 33406-33416.

38. McLean, K. J. & A. W. Munro, (2008)
Structural biology and biochemistry of cytochrome P450 systems in Mycobacterium tuberculosis.
Drug Metab Rev 40: 427-446.

39. Milano, A., M. R. Pasca, R. Provvedi, A. P. Lucarelli, G. Manina, A. Luisa de Jesus Lopes Ribeiro, R. Manganelli & G. Riccardi, (2008)
Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5 efflux system.
Tuberculosis (Edinb). [Epub ahead of print]

40. Neeli, R., M. Sabri, K. J. McLean, A. J. Dunford, N. S. Scrutton, D. Leys & A. W. Munro, (2008)
Trp(359) regulates flavin thermodynamics and coenzyme selectivity in Mycobacterium tuberculosis FprA.
Biochem J 411: 563-570.

41. Nordqvist, A., M. T. Nilsson, S. Rottger, L. R. Odell, W. W. Krajewski, C. Evalena Andersson, M. Larhed, S. L. Mowbray & A. Karlen, (2008)
Evaluation of the amino acid binding site of Mycobacterium tuberculosis glutamine synthetase for drug discovery.
Bioorg Med Chem 16: 5501-5513.

42. O'Hare, H. M., R. Duran, C. Cervenansky, M. Bellinzoni, A. M. Wehenkel, O. Pritsch, G. Obal, J. Baumgartner, J. Vialaret, K. Johnsson & P. M. Alzari, (2008)
Regulation of glutamate metabolism by protein kinases in mycobacteria.
Mol Microbiol 70: 1408-1423.

43. O'Hare, H. M., A. Juillerat, P. Dianiskova & K. Johnsson, (2008)
A split-protein sensor for studying protein-protein interaction with mycobacteria.
J Microbiol Methods 73: 79-84.

44. Riccardi, G., A. Milano, M. R. Pasca & D. H. Nies, (2008)
Genomic analysis of zinc homeostasis in Mycobacterium tuberculosis.
FEMS Microbiol Lett 287: 1-7.

45. Szekely, R., F. Waczek, I. Szabadkai, G. Nemeth, B. Hegymegi-Barakonyi, D. Eros, B. Szokol, J. Pato, D. Hafenbradl, J. Satchell, B. Saint-Joanis, S. T. Cole, L. Orfi, B. M. Klebl & G. Keri, (2008)
A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling.
Immunol Lett 116: 225-231.

46. Wehenkel, A., M. Bellinzoni, M. Grana, R. Duran, A. Villarino, P. Fernandez, G. Andre-Leroux, P. England, H. Takiff, C. Cervenansky, S. T. Cole & P. M. Alzari, (2008) Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential. Biochim Biophys Acta 1784: 193-202.


47. Aleksey M. Anuchin, Andrey L. Mulyukin, Natalya E. Suzina, Vitaly I. Duda, Galina I. El-Registan and Arseny Kaprelyants. Dormant forms of Mycobacterium smegmatis with distinct morphology (2009) Microbiology 155:1071-1079.

48. Aleksey M. Anuchin1, Anna V. Goncharenko1, Oxana Demidenok, , Andrey L. Mulyukin2 , M.Moisenovich, Arseny S. Kaprelyants. (2009) The model of dormant mycobacteria for testing of drugs against latent tuberculosis. Applied biochemistry and microbiology. In press

49. Bottai, D. & Brosch, R. (2009) Mycobacterial PE, PPE and ESX clusters: novel insights into the secretion of these most unusual protein families. Mol Microbiol 73, 325-8.

50. Bitter, W. et al. (2009) Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog 5, e1000507.

51. Carta F,. Maresca A., Covarrubias A.S., Mowbray S.L., Jones T.A., Supuran C.T. (2009) 'Carbonic anhydrase inhibitors. Characterization and inhibition studies of the most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c.' Bioorg. Med. Chem. Lett. 19 6649-54.

52. Demina G.R., Makarov V.A., Nikitushkin V.D., Ryabova O.B., Vostroknutova G.N., Salina E.G., Shleeva M.O., Goncharenko A.V., Kaprelyants A.S. (2009) Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity, PloS ONE, in press.

53. Forti, F., Crosta, A., Ghisotti, D. (2009). Pristinamycin-inducible gene regulation in mycobacteria. J. Biotechnol. 140: 270-277.

54. Gavalda, S., Léger, M., van der Rest, B., Stella, A., Bardou, F., Montrozier, H., Chalut, C., Burlet-Schiltz, O., Marrakchi, H., Daffé , M., and Quémard, A. (2009). The Pks13/FadD32 crosstalk for thebiosynthesis of mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem., 284: 19255-19264.

55. Léger, M., Gavalda, S., Guillet, V., van der Rest, B., Slama, N., Montrozier, H., Mourey, L., Quémard, A., Daffé, M., and Marrakchi, H. (2009). The Dual Function of the Mycobacterium tuberculosis FadD32 Required for Mycolic Acid Biosynthesis. Chem. Biol, 16: 510-519.

56. Maciag A, Piazza A, Riccardi G, Milano A. (2009) Transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis. BMC Microbiol. 9: 48.

57. Makarov, V., G. Manina, K. Mikusova, U. Mšllmann, O. Ryabova, B. Saint-Joanis, N. Dhar, M.R. Pasca, S. Buroni, A.P. Lucarelli, A. Milano, E. De Rossi, M. Belanova, A. Bobovska, P. Dianiskova, J. Kordulakova, C. Sala, E. Fullam, P. Schneider, J.D. McKinney, P. Brodin, T. Christophe, S. Waddell, P. Butcher, J. Albrethsen, I. Rosenkrands, R. Brosch, V. Nandi, S. Bharath, S. Gaonkar, R.K Shandil, V. Balasubramanian, T. Balganesh, S. Tyagi, J. Grosset, G. Riccardi and S.T. Cole (2009). Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis. Science; 324 (5928): 801-4.

58. Mariano, S., Roos, A.K., Mowbray, S.L. and Salmon, L. (2009) 'Competitive inhibitors of type B ribose- 5-phosphate isomerases: design, synthesis and kinetic evaluation of new D-allose and D-allulose 6- phosphate derivatives.' Carbohydrate Research 344: 869-80.

59. Milano A, Pasca MR, Provvedi R, Lucarelli AP, Manina G, de Jesus Lopes Ribeiro AL, Manganelli R, Riccardi G. (2009) Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5 efflux system. Tuberculosis (Edinb). 89: 84-90.

60. McLean, K.J., Lafite, P., Levy, C., Cheesman, M.R., Mast, N., Pikuleva, I.A., Leys, D. and Munro, A.W. (2009). The structure of Mycobacterium tuberculosis CYP125: Molecular basis for cholesterol binding in a P450 needed for host infection (in press).

61. Nilsson, M.T., Krajewski, W.W., Yellagunda, S., Prabhumurthy, Srinivasa, B.R, Yahiaoui, S., Larhed, M., Jones, T.A. and Mowbray, S.L. (2009) 'Structural basis of inhibition of Mycobacterium tuberculosis glutamine synthetase by novel ATP-competitive inhibitors.' J. Mol. Biol. 393: 504-513.

62. Nott, T.J., Kelly,G., Stach, L., Li, J., Westcott, S., Patel, D., Hunt, D.M., Howell, S., Buxton, R.S., O'Hare, H.M., & Smerdon, S.J. (2009) An Intramolecular Switch Regulates Phosphoindependent FHA Domain Interactions in Mycobacterium tuberculosis. Science Signaling 2: (63), ra12.

63. Odell, L.R., Nilsson, M.T., Gising, J., Lagerlund, O., Muthas, D., Nordqvist, A., Karlén, A., Larhed, M. (2009) 'Functionalized 3-Amino-imidazo[1,2-a]pyridines: A Novel Class of Drug-Like Mycobacterium tuberculosis Glutamine Synthetase Inhibitors.' Biorganic & Medicinal Chemistry Letters, accepted.

64. Riccardi G, Pasca MR, Buroni S. Mycobacterium tuberculosis: drug resistance and future perspectives. Future Microbiol. 2009. 4:597-614.

65. Sabri, M., A. J. Dunford, K. J. McLean, R. Neeli, N. S. Scrutton, D. Leys & A. W. Munro, (2009)
Characterization of coenzyme binding and selectivity determinants in Mycobacterium tuberculosis flavoprotein reductase A: analysis of Arg(199) and Arg(200) mutants at the NADP(H) 2'-phosphate binding site. Biochem J 417: 103-112.

66. Saint-Joanis, B. & Brosch, R. [A promising new class of antituberculous molecules]. (2009) Med Sci (Paris) 25: 663-5 .

67. Sala, C., A. Haouz, F. A. Saul, I. Miras, I. Rosenkrands, P. M. Alzari & S. T. Cole, (2009) Genomewide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis. Mol Microbiol 71: 1102-1116.

68. Sala, C., D. C. Grainger & S. T. Cole, (2009) Dissecting regulatory networks in host-pathogen interaction using chIP-on-chip technology. Cell Host Microbe 5: 430-437.

69. Serafini, A., Boldrin, F., Palù, G., Manganelli, R. (2009). Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc. J. Bacteriol. 191: 6340-6344.

70. Simeone, R., Bottai, D. & Brosch, R. (2009) ESX/type VII secretion systems and their role in hostpathogen interaction. Curr Opin Microbiol 12: 4-10.

71. Stokes, R. and Waddell, S. J (2009). Adjusting to a new home - Mycobacterium tuberculosis gene expression in response to an intracellular lifestyle. Accepted. Future Microbiology Reviews.

72. Waddell, S. J. & P. D. Butcher (2009). Intracellular expression profiling, in Intracellular Niches of Pathogens - A Microbe's Guide through the Host Cell (Schaible, U.E and Haas, A. eds.), Wiley-VCH Publishers.

73. Waddell, S. J. and P. D. Butcher (2009). Use of DNA arrays to study transcriptional responses to antimycobacterial compounds, in Antibiotic Resistance Protocols:Second Edition (Gillespie, S.H and McHugh, T.D. eds.), Humana Press Inc., Totowa, NJ.

74. Yoya, G. K., F. Bedos-Belval, P. Constant, H. Duran, M. Daffe & M. Baltas, (2009)
Synthesis and evaluation of a novel series of pseudo-cinnamic derivatives as antituberculosis agents.
Bioorg Med Chem Lett 19: 341-343.


5. Ingvarsson H., Unge T. (2010)
Flexibility and communication within the structure of the Mycobacterium smegmatis methionyl-tRNA synthetase.
FEBS J. 277: 3947-62.

76. Castell A., Mille C., Unge T. (2010)
Structural analysis of mycobacterial branched-chain aminotransferase: implications for inhibitor design.
Acta Cryst. D66: 549-57.

Related publications


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Epoxide hydrolases: structure, function, mechanism, and assay.
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Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis.
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