Structure-Activity Relationship Studies on the Macrolide Exotoxin Mycolactone of Mycobacterium ulcerans

PLoS Neglected Tropical Diseases

Volumn 7, Issue 3, 2013, Pages

  Scherr, Nicole ^a,b   Gersbach, Philipp ^c   Dangy, Jean Pierre ^a,b   Bomio, Claudio ^c   Li, Jun ^c   Altmann, Karl Heinz ^c   Pluschke, Gerd ^a,b  

^a SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

^c ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL TOXIN; MYCOLACTONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIMICROBIAL ACTIVITY; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; DISK DIFFUSION; FIBROBLAST; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; IC 50; LC 50; MYCOBACTERIUM ULCERANS; NECROSIS; NONHUMAN; STRUCTURE ACTIVITY RELATION;

EID: 84876007045     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0002143     Document Type: Article

References (41)

1. George KM, Chatterjee D, Gunawardana G, Welty D, Hayman J, et al. (1999) Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science 283: 854-857.
2. Sarfo FS, Phillips RO, Rangers B, Mahrous EA, Lee RE, et al. (2010) Detection of Mycolactone A/B in Mycobacterium ulcerans-Infected Human Tissue. PLoS Negl Trop Dis 4: e577.
3. Ranger B, Mahrous E, Mosi L, Adusumilli S, Lee R, et al. (2006) Globally distributed mycobacterial fish pathogens produce a novel plasmid-encoded toxic macrolide, mycolactone F. Infect Immun 74: 6037-6045.
4. Adusumilli S, Mve-Obiang A, Sparer T, Meyers W, Hayman J, et al. (2005) Mycobacterium ulcerans toxic macrolide, mycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo. Cell Microbiol 7: 1295-1304.
5. Snyder D, Small P, (2003) Uptake and cellular actions of mycolactone, a virulence determinant for Mycobacterium ulcerans. Microb Pathog 34: 91-101.
6. George KM, Pascopella L, Welty DM, Small PL, (2000) A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells. Infect Immun 68: 877-883.
7. Dobos K, Small P, Deslauriers M, Quinn F, King C, (2001) Mycobacterium ulcerans cytotoxicity in an adipose cell model. Infect Immun 69: 7182-7186.
8. Bozzo C, Tiberio R, Graziola F, Pertusi G, Valente G, et al. (2010) A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells. Microbes Infect 12: 1258-1263.
9. Houngbédji G, Côté C, Small P, Frenette J, (2009) Limited repair and structural damages displayed by skeletal muscles loaded with mycolactone. Microbes Infect 11: 238-244.
10. Houngbédji GM, Bouchard P, Frenette J, (2011) Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation. Am J Physiol Regul Integr Comp Physiol 300: R724-732.
11. Coutanceau E, Marsollier L, Brosch R, Perret E, Goossens P, et al. (2005) Modulation of the host immune response by a transient intracellular stage of Mycobacterium ulcerans: the contribution of endogenous mycolactone toxin. Cell Microbiol 7: 1187-1196.
12. Torrado E, Fraga AG, Castro AG, Stragier P, Meyers WM, et al. (2007) Evidence for an intramacrophage growth phase of Mycobacterium ulcerans. Infect Immun 75: 977-987.
13. Torrado E, Fraga AG, Logarinho E, Martins TG, Carmona JA, et al. (2010) IFN-gamma-dependent activation of macrophages during experimental infections by Mycobacterium ulcerans is impaired by the toxin mycolactone. J Immunol 184: 947-955.
14. Hong H, Coutanceau E, Leclerc M, Caleechurn L, Leadlay P, et al. (2008) Mycolactone Diffuses from Mycobacterium ulcerans-Infected Tissues and Targets Mononuclear Cells in Peripheral Blood and Lymphoid Organs. PLoS Negl Trop Dis 2: e325.
15. Coutanceau E, Decalf J, Martino A, Babon A, Winter N, et al. (2007) Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med 204: 1395-1403.
16. Fraga AG, Cruz A, Martins TG, Torrado E, Saraiva M, et al. (2011) Mycobacterium ulcerans triggers T-cell immunity followed by local and regional but not systemic immunosuppression. Infect Immun 79: 421-430.
17. Boulkroun S, Guenin-Macé L, Thoulouze MI, Monot M, Merckx A, et al. (2010) Mycolactone suppresses T cell responsiveness by altering both early signaling and posttranslational events. J Immunol 184: 1436-1444.
18. Guenin-Macé L, Carrette F, Asperti-Boursin F, Le Bon A, Caleechurn L, et al. (2011) Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression. Proc Natl Acad Sci U S A 108: 12833-12838.
19. Stinear TP, Mve-Obiang A, Small PL, Frigui W, Pryor MJ, et al. (2004) Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci U S A 101: 1345-1349.
20. Stinear TP, Pryor MJ, Porter JL, Cole ST, (2005) Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology 151: 683-692.
21. Yip M, Porter J, Fyfe J, Lavender C, Portaels F, et al. (2007) Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria from a common Mycobacterium marinum progenitor. J Bacteriol 189: 2021-2029.
22. Mve-Obiang A, Lee RE, Portaels F, Small PL, (2003) Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence. Infect Immun 71: 774-783.
23. Doig KD, Holt KE, Fyfe JA, Lavender CJ, Eddyani M, et al. (2012) On the origin of Mycobacterium ulcerans, the causative agent of buruli ulcer. BMC Genomics 13: 258.
24. Röltgen K, Stinear TP, Pluschke G, (2012) The genome, evolution and diversity of Mycobacterium ulcerans. Infect Genet Evol 12: 522-529.
25. Mve-Obiang A, Lee R, Portaels F, Small P, (2003) Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence. Infect Immun 71: 774-783.
26. Cadapan L, Arslanian R, Carney J, Zavala S, Small P, et al. (2001) Suspension cultivation of Mycobacterium ulcerans for the production of mycolactones. FEMS Microbiol Lett 205: 385-389.
27. Alexander M, Fontaine S, La Clair J, Dipasquale A, Rheingold A, et al. (2006) Synthesis of the mycolactone core by ring-closing metathesis. Chem Commun (Camb) pp. 4602-4604.
28. Benowitz A, Fidanze S, Small P, Kishi Y, (2001) Stereochemistry of the core structure of the mycolactones. J Am Chem Soc 123: 5128-5129.
29. Jackson KL, Li W, Chen CL, Kishi Y, (2010) Scalable and efficient synthesis of the mycolactone core. Tetrahedron 66: 2263-2272.
30. Ko KS, Alexander MD, Fontaine SD, Biggs-Houck JE, La Clair JJ, et al. (2010) Synthetic studies on the mycolactone core. Org Biomol Chem 8: 5159-5165.
31. Wang G, Yin N, Negishi E, (2011) Highly stereoselective total synthesis of fully hydroxy-protected mycolactones A and B and their stereoisomerization upon deprotection. Chemistry 17: 4118-4130.
32. Judd T, Bischoff A, Kishi Y, Adusumilli S, Small P, (2004) Structure determination of mycolactone C via total synthesis. Org Lett 6: 4901-4904.
33. Kim HJ, Kishi Y, (2008) Total synthesis and stereochemistry of mycolactone F. J Am Chem Soc 130: 1842-1844.
34. Chany AC, Casarotto V, Schmitt M, Tarnus C, Guenin-Macé L, et al. (2011) A diverted total synthesis of mycolactone analogues: an insight into Buruli ulcer toxins. Chemistry 17: 14413-14419.
35. Gersbach P, Jantsch A, Feyen F, Scherr N, Dangy JP, et al. (2011) A ring-closing metathesis (RCM)-based approach to mycolactones A/B. Chemistry 17: 13017-13031.
36. Hong H, Stinear T, Porter J, Demangel C, Leadlay PF, (2007) A novel mycolactone toxin obtained by biosynthetic engineering. Chembiochem 8: 2043-2047.
37. Kishi Y, (2011) Chemistry of mycolactones, the causative toxins of Buruli ulcer. Proc Natl Acad Sci U S A 108: 6703-6708.
38. Gersbach P, Jantsch A, Feyen F, Scherr N, Dangy JP, et al. (2011) A ring-closing metathesis (RCM)-based approach to mycolactones A/B. Chemistry 17: 13017-13031.
39. Snyder DS, Small PL, (2003) Uptake and cellular actions of mycolactone, a virulence determinant for Mycobacterium ulcerans. Microb Pathog 34: 91-101.
40. Pahlevan AA, Wright DJ, Andrews C, George KM, Small PL, et al. (1999) The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function. J Immunol 163: 3928-3935.
41. Simmonds R, Lali F, Smallie T, Small P, Foxwell B, (2009) Mycolactone inhibits monocyte cytokine production by a posttranscriptional mechanism. J Immunol 182: 2194-2202.