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Volume 160, Issue 8

The molecular biology of mycobacterial trehalose in the quest for advanced tuberculosis therapies Free

Abstract

Trehalose is a natural glucose disaccharide identified in the 19th century in fungi and insect cocoons, and later across the three domains of life. In members of the genus , which includes the tuberculosis (TB) pathogen and over 160 species of nontuberculous mycobacteria (NTM), many of which are opportunistic pathogens, trehalose has been an important focus of research over the last 60 years. It is a crucial player in the assembly and architecture of the remarkable mycobacterial cell envelope as an element of unique highly antigenic glycolipids, namely trehalose dimycolate (‘cord factor’). Free trehalose has been detected in the mycobacterial cytoplasm and occasionally in oligosaccharides with unknown function. TB and NTM infection statistics and death toll, the decline in immune responses in the aging population, human immunodeficiency virus/AIDS or other debilitating conditions, and the proliferation of strains with different levels of resistance to the dated drugs in use, all merge into a serious public-health threat urging more effective vaccines, efficient diagnostic tools and new drugs. This review deals with the latest findings on mycobacterial trehalose biosynthesis, catabolism, processing and recycling, as well with the ongoing quest for novel trehalose-related mechanisms to be targeted by novel TB therapeutics. In this context, the drug-discovery pipeline has recently included new lead compounds directed toward trehalose-related targets highlighting the potential of these pathways to stem the tide of rising drug resistance.

  • Published Online:
Funding
This study was supported by the:
  • Mizutani Foundation for Glycoscience, Japan
  • Fundação para a Ciência e a Tecnologia (FCT), Portugal
  • Programa Operacional Factores de Competitividade (POFC)
  • FEDER/COMPETE (Award PEst-C/SAU/LA0001/2013-2014, PTDC/BIA-MIC/2779/2012 and PTDC/BIA-BCM/112459/2009)
  • FCT (Award SFRH/BPD/79531/2011, SFRH/BD/74845/2010 and SFRH/BPD/43321/2008)
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2014-08-01
2024-04-24
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References

  1. Alarico S., Empadinhas N., Mingote A., Simões C., Santos M. S., da Costa M. S. ( 2007). Mannosylglycerate is essential for osmotic adjustment in Thermus thermophilus strains HB27 and RQ-1. Extremophiles 11:833–840 [View Article][PubMed]
     [Google Scholar]
  2. Alarico S., da Costa M. S., Empadinhas N. ( 2008). Molecular and physiological role of the trehalose-hydrolyzing alpha-glucosidase from Thermus thermophilus HB27. J Bacteriol 190:2298–2305 [View Article][PubMed]
     [Google Scholar]
  3. Alarico S., Empadinhas N., da Costa M. S. ( 2013). A new bacterial hydrolase specific for the compatible solutes α-D-mannopyranosyl-(1→2)-D-glycerate and α-D-glucopyranosyl-(1→2)-D-glycerate. Enzyme Microb Technol 52:77–83 [View Article][PubMed]
     [Google Scholar]
  4. Alibaud L., Pawelczyk J., Gannoun-Zaki L., Singh V. K., Rombouts Y., Drancourt M., Dziadek J., Guérardel Y., Kremer L. ( 2014). Increased phagocytosis of Mycobacterium marinum mutants defective in lipooligosaccharide production: a structure-activity relationship study. J Biol Chem 289:215–228 [View Article][PubMed]
     [Google Scholar]
  5. Andersen C. S., Agger E. M., Rosenkrands I., Gomes J. M., Bhowruth V., Gibson K. J., Petersen R. V., Minnikin D. E., Besra G. S., Andersen P. ( 2009). A simple mycobacterial monomycolated glycerol lipid has potent immunostimulatory activity. J Immunol 182:424–432 [View Article][PubMed]
     [Google Scholar]
  6. Anderson D. H., Harth G., Horwitz M. A., Eisenberg D. ( 2001). An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (antigen 85B), a mycolyl transferase. J Mol Biol 307:671–681 [View Article][PubMed]
     [Google Scholar]
  7. Armitige L. Y., Jagannath C., Wanger A. R., Norris S. J. ( 2000). Disruption of the genes encoding antigen 85A and antigen 85B of Mycobacterium tuberculosis H37Rv: effect on growth in culture and in macrophages. Infect Immun 68:767–778 [View Article][PubMed]
     [Google Scholar]
  8. Azad G. K., Singh V., Mandal P., Singh P., Golla U., Baranwal S., Chauhan S., Tomar R. S. ( 2014). Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity in Saccharomyces cerevisiae with inhibition of glutamate dehydrogenase being a target. FEBS Open Bio 4:77–89 [View Article][PubMed]
     [Google Scholar]
  9. Backus K. M., Boshoff H. I., Barry C. S., Boutureira O., Patel M. K., D’Hooge F., Lee S. S., Via L. E., Tahlan K. & other authors ( 2011). Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Nat Chem Biol 7:228–235 [View Article][PubMed]
     [Google Scholar]
  10. Barry C. S., Backus K. M., Barry C. E. III, Davis B. G. ( 2011). ESI-MS assay of M. tuberculosis cell wall antigen 85 enzymes permits substrate profiling and design of a mechanism-based inhibitor. J Am Chem Soc 133:13232–13235 [View Article][PubMed]
     [Google Scholar]
  11. Belisle J. T., Brennan P. J. ( 1989). Chemical basis of rough and smooth variation in mycobacteria. J Bacteriol 171:3465–3470[PubMed]
     [Google Scholar]
  12. Belisle J. T., Vissa V. D., Sievert T., Takayama K., Brennan P. J., Besra G. S. ( 1997). Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:1420–1422 [View Article][PubMed]
     [Google Scholar]
  13. Berthelot M. ( 1858). Sur le trehalose, nouvelle espéce de sucre. Compt Rend Hebd Seanc Acad Sci, Paris 46:1276–1279
     [Google Scholar]
  14. Besra G. S., McNeil M. R., Khoo K. H., Dell A., Morris H. R., Brennan P. J. ( 1993). Trehalose-containing lipooligosaccharides of Mycobacterium gordonae: presence of a mono-O-methyltetra-O-acyltrehalose “core” and branching in the oligosaccharide backbone. Biochemistry 32:12705–12714 [View Article][PubMed]
     [Google Scholar]
  15. Besra G. S., Khoo K. H., Belisle J. T., McNeil M. R., Morris H. R., Dell A., Brennan P. J. ( 1994). New pyruvylated, glycosylated acyltrehaloses from Mycobacterium smegmatis strains, and their implications for phage resistance in mycobacteria. Carbohydr Res 251:99–114 [View Article][PubMed]
     [Google Scholar]
  16. Bhatt K., Gurcha S. S., Bhatt A., Besra G. S., Jacobs W. R. Jr ( 2007). Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis. Microbiology 153:513–520 [View Article][PubMed]
     [Google Scholar]
  17. Biava M., Porretta G. C., Manetti F. ( 2007). New derivatives of BM212: a class of antimycobacterial compounds based on the pyrrole ring as a scaffold. Mini Rev Med Chem 7:65–78 [View Article][PubMed]
     [Google Scholar]
  18. Billi D., Potts M. ( 2002). Life and death of dried prokaryotes. Res Microbiol 153:7–12 [View Article][PubMed]
     [Google Scholar]
  19. Bloch H., Sorkin E., Erlenmeyer H. ( 1953). A toxic lipid component of the tubercle bacillus (cord factor). I. Isolation from petroleum ether extracts of young bacterial cultures. Am Rev Tuberc 67:629–643[PubMed]
     [Google Scholar]
  20. Brennan P. J. ( 1989). Structure of mycobacteria: recent developments in defining cell wall carbohydrates and proteins. Rev Infect Dis 11:Suppl. 2S420–S430 [View Article][PubMed]
     [Google Scholar]
  21. Burguière A., Hitchen P. G., Dover L. G., Kremer L., Ridell M., Alexander D. C., Liu J., Morris H. R., Minnikin D. E. & other authors ( 2005). LosA, a key glycosyltransferase involved in the biosynthesis of a novel family of glycosylated acyltrehalose lipooligosaccharides from Mycobacterium marinum. J Biol Chem 280:42124–42133 [View Article][PubMed]
     [Google Scholar]
  22. Cambier C. J., Takaki K. K., Larson R. P., Hernandez R. E., Tobin D. M., Urdahl K. B., Cosma C. L., Ramakrishnan L. ( 2014). Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature 505:218–222 [View Article][PubMed]
     [Google Scholar]
  23. Caner S., Nguyen N., Aguda A., Zhang R., Pan Y. T., Withers S. G., Brayer G. D. ( 2013). The structure of the Mycobacterium smegmatis trehalose synthase reveals an unusual active site configuration and acarbose-binding mode. Glycobiology 23:1075–1083 [View Article][PubMed]
     [Google Scholar]
  24. Cardoso F. S., Castro R. F., Borges N., Santos H. ( 2007). Biochemical and genetic characterization of the pathways for trehalose metabolism in Propionibacterium freudenreichii, and their role in stress response. Microbiology 153:270–280 [View Article][PubMed]
     [Google Scholar]
  25. Carroll J. D., Pastuszak I., Edavana V. K., Pan Y. T., Elbein A. D. ( 2007). A novel trehalase from Mycobacterium smegmatis - purification, properties, requirements. FEBS J 274:1701–1714 [View Article][PubMed]
     [Google Scholar]
  26. Chandra G., Chater K. F., Bornemann S. ( 2011). Unexpected and widespread connections between bacterial glycogen and trehalose metabolism. Microbiology 157:1565–1572 [View Article][PubMed]
     [Google Scholar]
  27. Chen W., Biswas T., Porter V. R., Tsodikov O. V., Garneau-Tsodikova S. ( 2011). Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB. Proc Natl Acad Sci U S A 108:9804–9808 [View Article][PubMed]
     [Google Scholar]
  28. Converse S. E., Mougous J. D., Leavell M. D., Leary J. A., Bertozzi C. R., Cox J. S. ( 2003). MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc Natl Acad Sci U S A 100:6121–6126 [View Article][PubMed]
     [Google Scholar]
  29. Crowe J. H., Hoekstra F. A., Crowe L. M. ( 1992). Anhydrobiosis. Annu Rev Physiol 54:579–599 [View Article][PubMed]
     [Google Scholar]
  30. Cruz-Hervert L. P., García-García L., Ferreyra-Reyes L., Bobadilla-del-Valle M., Cano-Arellano B., Canizales-Quintero S., Ferreira-Guerrero E., Báez-Saldaña R., Téllez-Vázquez N. & other authors ( 2012). Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes. Age Ageing 41:488–495 [View Article][PubMed]
     [Google Scholar]
  31. Daffe M., McNeil M., Brennan P. J. ( 1991). Novel type-specific lipooligosaccharides from Mycobacterium tuberculosis. Biochemistry 30:378–388 [View Article][PubMed]
     [Google Scholar]
  32. De Smet K. A., Weston A., Brown I. N., Young D. B., Robertson B. D. ( 2000). Three pathways for trehalose biosynthesis in mycobacteria. Microbiology 146:199–208[PubMed]
     [Google Scholar]
  33. Deidda D., Lampis G., Fioravanti R., Biava M., Porretta G. C., Zanetti S., Pompei R. ( 1998). Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 42:3035–3037[PubMed]
     [Google Scholar]
  34. Devulder G., Pérouse de Montclos M., Flandrois J. P. ( 2005). A multigene approach to phylogenetic analysis using the genus Mycobacterium as a model. Int J Syst Evol Microbiol 55:293–302 [View Article][PubMed]
     [Google Scholar]
  35. Dhiman R. K., Dinadayala P., Ryan G. J., Lenaerts A. J., Schenkel A. R., Crick D. C. ( 2011). Lipoarabinomannan localization and abundance during growth of Mycobacterium smegmatis. J Bacteriol 193:5802–5809 [View Article][PubMed]
     [Google Scholar]
  36. Dias M. V., Snee W. C., Bromfield K. M., Payne R. J., Palaninathan S. K., Ciulli A., Howard N. I., Abell C., Sacchettini J. C., Blundell T. L. ( 2011). Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis. Biochem J 436:729–739 [View Article][PubMed]
     [Google Scholar]
  37. Djonović S., Urbach J. M., Drenkard E., Bush J., Feinbaum R., Ausubel J. L., Traficante D., Risech M., Kocks C. & other authors ( 2013). Trehalose biosynthesis promotes Pseudomonas aeruginosa pathogenicity in plants. PLoS Pathog 9:e1003217 [View Article][PubMed]
     [Google Scholar]
  38. Doherty T. M. ( 2012). Immunotherapy for TB. Immunotherapy 4:629–647 [View Article][PubMed]
     [Google Scholar]
  39. Domenech P., Reed M. B., Barry C. E. III ( 2005). Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect Immun 73:3492–3501 [View Article][PubMed]
     [Google Scholar]
  40. Dubey V. S., Sirakova T. D., Kolattukudy P. E. ( 2002). Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. Mol Microbiol 45:1451–1459 [View Article][PubMed]
     [Google Scholar]
  41. Edavana V. K., Pastuszak I., Carroll J. D., Thampi P., Abraham E. C., Elbein A. D. ( 2004). Cloning and expression of the trehalose-phosphate phosphatase of Mycobacterium tuberculosis: comparison to the enzyme from Mycobacterium smegmatis. Arch Biochem Biophys 426:250–257 [View Article][PubMed]
     [Google Scholar]
  42. Ehrt S., Schnappinger D. ( 2009). Mycobacterial survival strategies in the phagosome: defence against host stresses. Cell Microbiol 11:1170–1178 [View Article][PubMed]
     [Google Scholar]
  43. Eis C., Watkins M., Prohaska T., Nidetzky B. ( 2001). Fungal trehalose phosphorylase: kinetic mechanism, pH-dependence of the reaction and some structural properties of the enzyme from Schizophyllum commune. Biochem J 356:757–767 [View Article][PubMed]
     [Google Scholar]
  44. Elbein A. D., Mitchell M. ( 1974). Effects of polyanions and polycations on the trehalose phosphate synthetase of Mycobacterium smegmatis. Carbohydr Res 37:223–238 [View Article][PubMed]
     [Google Scholar]
  45. Elbein A. D., Pan Y. T., Pastuszak I., Carroll D. ( 2003). New insights on trehalose: a multifunctional molecule. Glycobiology 13:17R–27R [View Article][PubMed]
     [Google Scholar]
  46. Elbein A. D., Pastuszak I., Tackett A. J., Wilson T., Pan Y. T. ( 2010). Last step in the conversion of trehalose to glycogen: a mycobacterial enzyme that transfers maltose from maltose 1-phosphate to glycogen. J Biol Chem 285:9803–9812 [View Article][PubMed]
     [Google Scholar]
  47. Etienne G., Malaga W., Laval F., Lemassu A., Guilhot C., Daffé M. ( 2009). Identification of the polyketide synthase involved in the biosynthesis of the surface-exposed lipooligosaccharides in mycobacteria. J Bacteriol 191:2613–2621 [View Article][PubMed]
     [Google Scholar]
  48. Falkinham J. O. III ( 2009). Surrounded by mycobacteria: nontuberculous mycobacteria in the human environment. J Appl Microbiol 107:356–367 [View Article][PubMed]
     [Google Scholar]
  49. Favrot L., Ronning D. R. ( 2012). Targeting the mycobacterial envelope for tuberculosis drug development. Expert Rev Anti Infect Ther 10:1023–1036 [View Article][PubMed]
     [Google Scholar]
  50. Favrot L., Grzegorzewicz A. E., Lajiness D. H., Marvin R. K., Boucau J., Isailovic D., Jackson M., Ronning D. R. ( 2013). Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen. Nat Commun 4:2748 [View Article][PubMed]
     [Google Scholar]
  51. Fitzpatrick D. A. ( 2009). Lines of evidence for horizontal gene transfer of a phenazine producing operon into multiple bacterial species. J Mol Evol 68:171–185 [View Article][PubMed]
     [Google Scholar]
  52. Flynn J. L., Chan J. ( 2005). What’s good for the host is good for the bug. Trends Microbiol 13:98–102 [View Article][PubMed]
     [Google Scholar]
  53. Freeman B. C., Chen C., Beattie G. A. ( 2010). Identification of the trehalose biosynthetic loci of Pseudomonas syringae and their contribution to fitness in the phyllosphere. Environ Microbiol 12:1486–1497[PubMed]
     [Google Scholar]
  54. Fujita Y., Naka T., McNeil M. R., Yano I. ( 2005). Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry. Microbiology 151:3403–3416 [View Article][PubMed]
     [Google Scholar]
  55. Furukawa A., Kamishikiryo J., Mori D., Toyonaga K., Okabe Y., Toji A., Kanda R., Miyake Y., Ose T. & other authors ( 2013). Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL. Proc Natl Acad Sci U S A 110:17438–17443 [View Article][PubMed]
     [Google Scholar]
  56. Geerdink D., Minnaard A. J. ( 2014). Total synthesis of sulfolipid-1. Chem Commun (Camb) 50:2286–2288 [View Article][PubMed]
     [Google Scholar]
  57. Gilmore S. A., Schelle M. W., Holsclaw C. M., Leigh C. D., Jain M., Cox J. S., Leary J. A., Bertozzi C. R. ( 2012). Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human macrophages. ACS Chem Biol 7:863–870 [View Article][PubMed]
     [Google Scholar]
  58. Glickman M. S. ( 2008). Cording, cord factors, and trehalose dimycolate. The Mycobacterial Cell Envelope63–73 Daffé M., Reyrat J. M. Washington, DC: American Society for Microbiology;
     [Google Scholar]
  59. Gobec S., Plantan I., Mravljak J., Svajger U., Wilson R. A., Besra G. S., Soares S. L., Appelberg R., Kikelj D. ( 2007). Design, synthesis, biochemical evaluation and antimycobacterial action of phosphonate inhibitors of antigen 85C, a crucial enzyme involved in biosynthesis of the mycobacterial cell wall. Eur J Med Chem 42:54–63 [View Article][PubMed]
     [Google Scholar]
  60. Griffin J. E., Gawronski J. D., Dejesus M. A., Ioerger T. R., Akerley B. J., Sassetti C. M. ( 2011). High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog 7:e1002251 [View Article][PubMed]
     [Google Scholar]
  61. Grzegorzewicz A. E., Pham H., Gundi V. A., Scherman M. S., North E. J., Hess T., Jones V., Gruppo V., Born S. E. & other authors ( 2012). Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol 8:334–341 [View Article][PubMed]
     [Google Scholar]
  62. Guenin-Macé L., Siméone R., Demangel C. ( 2009). Lipids of pathogenic mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis 56:255–268 [View Article][PubMed]
     [Google Scholar]
  63. Guiard J., Collmann A., Garcia-Alles L. F., Mourey L., Brando T., Mori L., Gilleron M., Prandi J., De Libero G., Puzo G. ( 2009). Fatty acyl structures of Mycobacterium tuberculosis sulfoglycolipid govern T cell response. J Immunol 182:7030–7037 [View Article][PubMed]
     [Google Scholar]
  64. Harland C. W., Rabuka D., Bertozzi C. R., Parthasarathy R. ( 2008). The Mycobacterium tuberculosis virulence factor trehalose dimycolate imparts desiccation resistance to model mycobacterial membranes. Biophys J 94:4718–4724 [View Article][PubMed]
     [Google Scholar]
  65. Harth G., Zamecnik P. C., Tabatadze D., Pierson K., Horwitz M. A. ( 2007). Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 104:7199–7204 [View Article][PubMed]
     [Google Scholar]
  66. Hartkoorn R. C., Pojer F., Read J. A., Gingell H., Neres J., Horlacher O. P., Altmann K. H., Cole S. T. ( 2014). Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA. Nat Chem Biol 10:96–98 [View Article][PubMed]
     [Google Scholar]
  67. Hatzios S. K., Schelle M. W., Holsclaw C. M., Behrens C. R., Botyanszki Z., Lin F. L., Carlson B. L., Kumar P., Leary J. A., Bertozzi C. R. ( 2009). PapA3 is an acyltransferase required for polyacyltrehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem 284:12745–12751 [View Article][PubMed]
     [Google Scholar]
  68. Hegde S. S., Vetting M. W., Roderick S. L., Mitchenall L. A., Maxwell A., Takiff H. E., Blanchard J. S. ( 2005). A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 308:1480–1483 [View Article][PubMed]
     [Google Scholar]
  69. Hoefsloot W., van Ingen J., Andrejak C., Angeby K., Bauriaud R., Bemer P., Beylis N., Boeree M. J., Cacho J. & other authors ( 2013). The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J 42:1604–1613 [View Article][PubMed]
     [Google Scholar]
  70. Hunter S. W., Murphy R. C., Clay K., Goren M. B., Brennan P. J. ( 1983). Trehalose-containing lipooligosaccharides. A new class of species-specific antigens from Mycobacterium. J Biol Chem 258:10481–10487[PubMed]
     [Google Scholar]
  71. Ibrahim D. A., Boucau J., Lajiness D. H., Veleti S. K., Trabbic K. R., Adams S. S., Ronning D. R., Sucheck S. J. ( 2012). Design, synthesis, and X-ray analysis of a glycoconjugate bound to Mycobacterium tuberculosis antigen 85C. Bioconjug Chem 23:2403–2416 [View Article][PubMed]
     [Google Scholar]
  72. Ishikawa E., Ishikawa T., Morita Y. S., Toyonaga K., Yamada H., Takeuchi O., Kinoshita T., Akira S., Yoshikai Y., Yamasaki S. ( 2009). Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206:2879–2888 [View Article][PubMed]
     [Google Scholar]
  73. Iturriaga G., Suárez R., Nova-Franco B. ( 2009). Trehalose metabolism: from osmoprotection to signaling. Int J Mol Sci 10:3793–3810 [View Article][PubMed]
     [Google Scholar]
  74. Jackson M., Raynaud C., Lanéelle M. A., Guilhot C., Laurent-Winter C., Ensergueix D., Gicquel B., Daffé M. ( 1999). Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope. Mol Microbiol 31:1573–1587 [View Article][PubMed]
     [Google Scholar]
  75. Jackson M., Stadthagen G., Gicquel B. ( 2007). Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: biosynthesis, transport, regulation and biological activities. Tuberculosis (Edinb) 87:78–86 [View Article][PubMed]
     [Google Scholar]
  76. Jackson M., McNeil M. R., Brennan P. J. ( 2013). Progress in targeting cell envelope biogenesis in Mycobacterium tuberculosis. Future Microbiol 8:855–875 [View Article][PubMed]
     [Google Scholar]
  77. Jankute M., Grover S., Rana A. K., Besra G. S. ( 2012). Arabinogalactan and lipoarabinomannan biosynthesis: structure, biogenesis and their potential as drug targets. Future Microbiol 7:129–147 [View Article][PubMed]
     [Google Scholar]
  78. Julián E., Roldán M., Sánchez-Chardi A., Astola O., Agustí G., Luquin M. ( 2010). Microscopic cords, a virulence-related characteristic of Mycobacterium tuberculosis, are also present in nonpathogenic mycobacteria. J Bacteriol 192:1751–1760 [View Article][PubMed]
     [Google Scholar]
  79. Kalscheuer R., Syson K., Veeraraghavan U., Weinrick B., Biermann K. E., Liu Z., Sacchettini J. C., Besra G., Bornemann S., Jacobs W. R. Jr ( 2010a). Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. Nat Chem Biol 6:376–384 [View Article][PubMed]
     [Google Scholar]
  80. Kalscheuer R., Weinrick B., Veeraraghavan U., Besra G. S., Jacobs W. R. Jr ( 2010b). Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 107:21761–21766 [View Article][PubMed]
     [Google Scholar]
  81. Kandror O., DeLeon A., Goldberg A. L. ( 2002). Trehalose synthesis is induced upon exposure of Escherichia coli to cold and is essential for viability at low temperatures. Proc Natl Acad Sci U S A 99:9727–9732 [View Article][PubMed]
     [Google Scholar]
  82. Kaur D., Guerin M. E., Skovierová H., Brennan P. J., Jackson M. ( 2009). Chapter 2. Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Adv Appl Microbiol 69:23–78 [View Article][PubMed]
     [Google Scholar]
  83. Khan A. A., Kamena F., Timmer M. S., Stocker B. L. ( 2013). Development of a benzophenone and alkyne functionalised trehalose probe to study trehalose dimycolate binding proteins. Org Biomol Chem 11:881–885 [View Article][PubMed]
     [Google Scholar]
  84. Klotzsche M., Ehrt S., Schnappinger D. ( 2009). Improved tetracycline repressors for gene silencing in mycobacteria. Nucleic Acids Res 37:1778–1788 [View Article][PubMed]
     [Google Scholar]
  85. Koester D. C., Awan S. I., Werz D. B. ( 2011). Hot on the trail of trehalose: a carbohydrate-based method for imaging Mycobacterium tuberculosis. ChemioCchem 12:1975–1977 [View Article][PubMed]
     [Google Scholar]
  86. Korf J., Stoltz A., Verschoor J., De Baetselier P., Grooten J. ( 2005). The Mycobacterium tuberculosis cell wall component mycolic acid elicits pathogen-associated host innate immune responses. Eur J Immunol 35:890–900 [View Article][PubMed]
     [Google Scholar]
  87. Kumar P., Schelle M. W., Jain M., Lin F. L., Petzold C. J., Leavell M. D., Leary J. A., Cox J. S., Bertozzi C. R. ( 2007). PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. Proc Natl Acad Sci U S A 104:11221–11226 [View Article][PubMed]
     [Google Scholar]
  88. La Rosa V., Poce G., Canseco J. O., Buroni S., Pasca M. R., Biava M., Raju R. M., Porretta G. C., Alfonso S. & other authors ( 2012). MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob Agents Chemother 56:324–331 [View Article][PubMed]
     [Google Scholar]
  89. Lang R. ( 2013). Recognition of the mycobacterial cord factor by Mincle: relevance for granuloma formation and resistance to tuberculosis. Front Immunol 4:5 [View Article][PubMed]
     [Google Scholar]
  90. Lee J. H., Lee K. H., Kim C. G., Lee S. Y., Kim G. J., Park Y. H., Chung S. O. ( 2005). Cloning and expression of a trehalose synthase from Pseudomonas stutzeri CJ38 in Escherichia coli for the production of trehalose. Appl Microbiol Biotechnol 68:213–219 [View Article][PubMed]
     [Google Scholar]
  91. Lee J., Repasy T., Papavinasasundaram K., Sassetti C., Kornfeld H. ( 2011). Mycobacterium tuberculosis induces an atypical cell death mode to escape from infected macrophages. PLoS ONE 6:e18367 [View Article][PubMed]
     [Google Scholar]
  92. Lee J., Lin E. W., Lau U. Y., Hedrick J. L., Bat E., Maynard H. D. ( 2013). Trehalose glycopolymers as excipients for protein stabilization. Biomacromolecules 14:2561–2569 [View Article][PubMed]
     [Google Scholar]
  93. Legendre D. P., Muzny C. A., Swiatlo E. ( 2012). Hansen’s disease (leprosy): current and future pharmacotherapy and treatment of disease-related immunologic reactions. Pharmacotherapy 32:27–37 [View Article][PubMed]
     [Google Scholar]
  94. Lew J. M., Kapopoulou A., Jones L. M., Cole S. T. ( 2011). TubercuList–10 years after. Tuberculosis (Edinb) 91:1–7 [View Article][PubMed]
     [Google Scholar]
  95. Li K., Schurig-Briccio L. A., Feng X., Upadhyay A., Pujari V., Lechartier B., Fontes F. L., Yang H., Rao G. & other authors ( 2014). Multitarget drug discovery for tuberculosis and other infectious diseases. J Med Chem 57:3126–3139 [View Article][PubMed]
     [Google Scholar]
  96. Liebl M., Nelius V., Kamp G., Ando O., Wegener G. ( 2010). Fate and effects of the trehalase inhibitor trehazolin in the migratory locust (Locusta migratoria). J Insect Physiol 56:567–574 [View Article][PubMed]
     [Google Scholar]
  97. Lu H., Zhu Z., Dong L., Jia X., Sun X., Yan L., Chai Y., Jiang Y., Cao Y. ( 2011). Lack of trehalose accelerates H2O2-induced Candida albicans apoptosis through regulating Ca2+ signaling pathway and caspase activity. PLoS ONE 6:e15808 [View Article][PubMed]
     [Google Scholar]
  98. Lun S., Guo H., Onajole O. K., Pieroni M., Gunosewoyo H., Chen G., Tipparaju S. K., Ammerman N. C., Kozikowski A. P., Bishai W. R. ( 2013). Indoleamides are active against drug-resistant Mycobacterium tuberculosis. Nat Commun 4:2907 [View Article][PubMed]
     [Google Scholar]
  99. Marrakchi H., Lanéelle M. A., Daffé M. ( 2014). Mycolic acids: structures, biosynthesis, and beyond. Chem Biol 21:67–85 [View Article][PubMed]
     [Google Scholar]
  100. Matsunaga I., Naka T., Talekar R. S., McConnell M. J., Katoh K., Nakao H., Otsuka A., Behar S. M., Yano I. & other authors ( 2008). Mycolyltransferase-mediated glycolipid exchange in mycobacteria. J Biol Chem 283:28835–28841 [View Article][PubMed]
     [Google Scholar]
  101. Mendes V., Maranha A., Lamosa P., da Costa M. S., Empadinhas N. ( 2010). Biochemical characterization of the maltokinase from Mycobacterium bovis BCG. BMC Biochem 11:21 [View Article][PubMed]
     [Google Scholar]
  102. Miah F., Koliwer-Brandl H., Rejzek M., Field R. A., Kalscheuer R., Bornemann S. ( 2013). Flux through trehalose synthase flows from trehalose to the alpha anomer of maltose in mycobacteria. Chem Biol 20:487–493 [View Article][PubMed]
     [Google Scholar]
  103. Middlebrook G., Coleman C. M., Schaefer W. B. ( 1959). Sulfolipid from virulent tubercle bacilli. Proc Natl Acad Sci U S A 45:1801–1804 [View Article][PubMed]
     [Google Scholar]
  104. Migliardo F., Salmeron C., Bayan N. ( 2014). Mobility and temperature resistance of trehalose mycolates as key characteristics of the outer membrane of Mycobacterium tuberculosis. J Biomol Struct Dyn [View Article][PubMed]
     [Google Scholar]
  105. Miller C. D., Hall K., Liang Y. N., Nieman K., Sorensen D., Issa B., Anderson A. J., Sims R. C. ( 2004). Isolation and characterization of polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates from soil. Microb Ecol 48:230–238 [View Article][PubMed]
     [Google Scholar]
  106. Minnikin D. E., Kremer L., Dover L. G., Besra G. S. ( 2002). The methyl-branched fortifications of Mycobacterium tuberculosis. Chem Biol 9:545–553 [View Article][PubMed]
     [Google Scholar]
  107. Mishra A. K., Driessen N. N., Appelmelk B. J., Besra G. S. ( 2011). Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev 35:1126–1157 [View Article][PubMed]
     [Google Scholar]
  108. Miyake Y., Toyonaga K., Mori D., Kakuta S., Hoshino Y., Oyamada A., Yamada H., Ono K., Suyama M. & other authors ( 2013). C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor. Immunity 38:1050–1062 [View Article][PubMed]
     [Google Scholar]
  109. Morbidoni H. R., Vilchèze C., Kremer L., Bittman R., Sacchettini J. C., Jacobs W. R. Jr ( 2006). Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids. Chem Biol 13:297–307 [View Article][PubMed]
     [Google Scholar]
  110. Mougous J. D., Petzold C. J., Senaratne R. H., Lee D. H., Akey D. L., Lin F. L., Munchel S. E., Pratt M. R., Riley L. W. & other authors ( 2004). Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Nat Struct Mol Biol 11:721–729 [View Article][PubMed]
     [Google Scholar]
  111. Mullis S. N., Falkinham J. O. III ( 2013). Adherence and biofilm formation of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium abscessus to household plumbing materials. J Appl Microbiol 115:908–914 [View Article][PubMed]
     [Google Scholar]
  112. Murphy H. N., Stewart G. R., Mischenko V. V., Apt A. S., Harris R., McAlister M. S., Driscoll P. C., Young D. B., Robertson B. D. ( 2005). The OtsAB pathway is essential for trehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem 280:14524–14529 [View Article][PubMed]
     [Google Scholar]
  113. Narumi K., Tsumita T. ( 1964). Isolation of a new polymer of α,α-trehalose 6,6'-diphosphate from Mycobacterium tuberculosis. Jpn J Exp Med 34:375–377[PubMed]
     [Google Scholar]
  114. Narumi K., Tsumita T. ( 1965). The isolation and identification of α,α-trehalose 6,6'-diphosphate, a subunit of the phosphorylated polysaccharide of Mycobacterium tuberculosis. J Biol Chem 240:2271–2276[PubMed]
     [Google Scholar]
  115. Narumi K., Tsumita T. ( 1967). Identification of α,α-trehalose 6,6′-dimannosylphosphate and α-maltose 1-phosphate of Mycobacteria. J Biol Chem 242:2233–2239[PubMed]
     [Google Scholar]
  116. Nessar R., Reyrat J. M., Davidson L. B., Byrd T. F. ( 2011). Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response. Microbiology 157:1187–1195 [View Article][PubMed]
     [Google Scholar]
  117. Nessar R., Cambau E., Reyrat J. M., Murray A., Gicquel B. ( 2012). Mycobacterium abscessus: a new antibiotic nightmare. J Antimicrob Chemother 67:810–818 [View Article][PubMed]
     [Google Scholar]
  118. Nguyen L., Chinnapapagari S., Thompson C. J. ( 2005). FbpA-dependent biosynthesis of trehalose dimycolate is required for the intrinsic multidrug resistance, cell wall structure, and colonial morphology of Mycobacterium smegmatis. J Bacteriol 187:6603–6611 [View Article][PubMed]
     [Google Scholar]
  119. Nobre A., Alarico S., Fernandes C., Empadinhas N., da Costa M. S. ( 2008). A unique combination of genetic systems for the synthesis of trehalose in Rubrobacter xylanophilus: properties of a rare actinobacterial TreT. J Bacteriol 190:7939–7946 [View Article][PubMed]
     [Google Scholar]
  120. Ohta M., Pan Y. T., Laine R. A., Elbein A. D. ( 2002). Trehalose-based oligosaccharides isolated from the cytoplasm of Mycobacterium smegmatis: relation to trehalose-based oligosaccharides attached to lipid. Eur J Biochem 269:3142–3149 [View Article][PubMed]
     [Google Scholar]
  121. Ojha A. K., Trivelli X., Guerardel Y., Kremer L., Hatfull G. F. ( 2010). Enzymatic hydrolysis of trehalose dimycolate releases free mycolic acids during mycobacterial growth in biofilms. J Biol Chem 285:17380–17389 [View Article][PubMed]
     [Google Scholar]
  122. Pan Y. T., Elbein A. D. ( 1996). Inhibition of the trehalose-P synthase of mycobacteria by various antibiotics. Arch Biochem Biophys 335:258–266 [View Article][PubMed]
     [Google Scholar]
  123. Pan Y. T., Koroth Edavana V., Jourdian W. J., Edmondson R., Carroll J. D., Pastuszak I., Elbein A. D. ( 2004). Trehalose synthase of Mycobacterium smegmatis: purification, cloning, expression, and properties of the enzyme. Eur J Biochem 271:4259–4269 [View Article][PubMed]
     [Google Scholar]
  124. Pan Y. T., Carroll J. D., Asano N., Pastuszak I., Edavana V. K., Elbein A. D. ( 2008). Trehalose synthase converts glycogen to trehalose. FEBS J 275:3408–3420 [View Article][PubMed]
     [Google Scholar]
  125. Pangborn M. C., Anderson R. J. ( 1933). The chemistry of the lipids of tubercle bacilli: XXXII. isolation of trehalose from the timothy-grass bacillus. J Biol Chem 101:105–109
     [Google Scholar]
  126. Poce G., Bates R. H., Alfonso S., Cocozza M., Porretta G. C., Ballell L., Rullas J., Ortega F., De Logu A. & other authors ( 2013). Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection. PLoS ONE 8:e56980 [View Article][PubMed]
     [Google Scholar]
  127. Protopopova M., Hanrahan C., Nikonenko B., Samala R., Chen P., Gearhart J., Einck L., Nacy C. A. ( 2005). Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J Antimicrob Chemother 56:968–974 [View Article][PubMed]
     [Google Scholar]
  128. Puech V., Guilhot C., Perez E., Tropis M., Armitige L. Y., Gicquel B., Daffé M. ( 2002). Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis. Mol Microbiol 44:1109–1122 [View Article][PubMed]
     [Google Scholar]
  129. Rao S. P., Lakshminarayana S. B., Kondreddi R. R., Herve M., Camacho L. R., Bifani P., Kalapala S. K., Jiricek J., Ma N. L. & other authors ( 2013). Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis. Sci Transl Med 5:214ra168 [View Article][PubMed]
     [Google Scholar]
  130. Rayasam G. V. ( 2014). MmpL3 a potential new target for development of novel anti-tuberculosis drugs. Expert Opin Ther Targets 18:247–256 [View Article][PubMed]
     [Google Scholar]
  131. Remuiñán M. J., Pérez-Herrán E., Rullás J., Alemparte C., Martínez-Hoyos M., Dow D. J., Afari J., Mehta N., Esquivias J. & other authors ( 2013). Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6′,7′-dihydrospiro[piperidine-4,4′-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3. PLoS ONE 8:e60933 [View Article][PubMed]
     [Google Scholar]
  132. Ren H., Dover L. G., Islam S. T., Alexander D. C., Chen J. M., Besra G. S., Liu J. ( 2007). Identification of the lipooligosaccharide biosynthetic gene cluster from Mycobacterium marinum. Mol Microbiol 63:1345–1359 [View Article][PubMed]
     [Google Scholar]
  133. Rengarajan J., Bloom B. R., Rubin E. J. ( 2005). Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci U S A 102:8327–8332 [View Article][PubMed]
     [Google Scholar]
  134. Rombouts Y., Burguière A., Maes E., Coddeville B., Elass E., Guérardel Y., Kremer L. ( 2009). Mycobacterium marinum lipooligosaccharides are unique caryophyllose-containing cell wall glycolipids that inhibit tumor necrosis factor-alpha secretion in macrophages. J Biol Chem 284:20975–20988 [View Article][PubMed]
     [Google Scholar]
  135. Rombouts Y., Elass E., Biot C., Maes E., Coddeville B., Burguière A., Tokarski C., Buisine E., Trivelli X. & other authors ( 2010). Structural analysis of an unusual bioactive N-acylated lipo-oligosaccharide LOS-IV in Mycobacterium marinum. J Am Chem Soc 132:16073–16084 [View Article][PubMed]
     [Google Scholar]
  136. Rombouts Y., Alibaud L., Carrère-Kremer S., Maes E., Tokarski C., Elass E., Kremer L., Guérardel Y. ( 2011). Fatty acyl chains of Mycobacterium marinum lipooligosaccharides: structure, localization and acylation by PapA4 (MMAR_2343) protein. J Biol Chem 286:33678–33688 [View Article][PubMed]
     [Google Scholar]
  137. Ronning D. R., Vissa V., Besra G. S., Belisle J. T., Sacchettini J. C. ( 2004). Mycobacterium tuberculosis antigen 85A and 85C structures confirm binding orientation and conserved substrate specificity. J Biol Chem 279:36771–36777 [View Article][PubMed]
     [Google Scholar]
  138. Rønnow T. E., Meldal M., Bock K. ( 1994). Gram-scale synthesis of alpha,alpha-trehalose 6-monophosphate and alpha,alpha-trehalose 6,6′-diphosphate. Carbohydr Res 260:323–328 [View Article][PubMed]
     [Google Scholar]
  139. Rose J. D., Maddry J. A., Comber R. N., Suling W. J., Wilson L. N., Reynolds R. C. ( 2002). Synthesis and biological evaluation of trehalose analogs as potential inhibitors of mycobacterial cell wall biosynthesis. Carbohydr Res 337:105–120 [View Article][PubMed]
     [Google Scholar]
  140. Rosenkrands I., Agger E. M., Olsen A. W., Korsholm K. S., Andersen C. S., Jensen K. T., Andersen P. ( 2005). Cationic liposomes containing mycobacterial lipids: a new powerful Th1 adjuvant system. Infect Immun 73:5817–5826 [View Article][PubMed]
     [Google Scholar]
  141. Rousseau C., Neyrolles O., Bordat Y., Giroux S., Sirakova T. D., Prevost M. C., Kolattukudy P. E., Gicquel B., Jackson M. ( 2003). Deficiency in mycolipenate- and mycosanoate-derived acyltrehaloses enhances early interactions of Mycobacterium tuberculosis with host cells. Cell Microbiol 5:405–415 [View Article][PubMed]
     [Google Scholar]
  142. Roy R., Usha V., Kermani A., Scott D. J., Hyde E. I., Besra G. S., Alderwick L. J., Fütterer K. ( 2013). Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2. ACS Chem Biol 8:2245–2255 [View Article][PubMed]
     [Google Scholar]
  143. Rozwarski D. A., Grant G. A., Barton D. H., Jacobs W. R. Jr, Sacchettini J. C. ( 1998). Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 279:98–102 [View Article][PubMed]
     [Google Scholar]
  144. Saadat S., Ballou C. E. ( 1983). Pyruvylated glycolipids from Mycobacterium smegmatis. Structures of two oligosaccharide components. J Biol Chem 258:1813–1818[PubMed]
     [Google Scholar]
  145. Sacksteder K. A., Protopopova M., Barry C. E. III, Andries K., Nacy C. A. ( 2012). Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action. Future Microbiol 7:823–837 [View Article][PubMed]
     [Google Scholar]
  146. Sakamoto K., Kim M. J., Rhoades E. R., Allavena R. E., Ehrt S., Wainwright H. C., Russell D. G., Rohde K. H. ( 2013). Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases. Infect Immun 81:764–776 [View Article][PubMed]
     [Google Scholar]
  147. Sanki A. K., Boucau J., Umesiri F. E., Ronning D. R., Sucheck S. J. ( 2009). Design, synthesis and biological evaluation of sugar-derived esters, alpha-ketoesters and alpha-ketoamides as inhibitors for Mycobacterium tuberculosis antigen 85C. Mol Biosyst 5:945–956 [View Article][PubMed]
     [Google Scholar]
  148. Sarkar D., Sidhu M., Singh A., Chen J., Lammas D. A., van der Sar A. M., Besra G. S., Bhatt A. ( 2011). Identification of a glycosyltransferase from Mycobacterium marinum involved in addition of a caryophyllose moiety in lipooligosaccharides. J Bacteriol 193:2336–2340 [View Article][PubMed]
     [Google Scholar]
  149. Schoenen H., Bodendorfer B., Hitchens K., Manzanero S., Werninghaus K., Nimmerjahn F., Agger E. M., Stenger S., Andersen P. & other authors ( 2010). Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 184:2756–2760 [View Article][PubMed]
     [Google Scholar]
  150. Seeliger J. C., Holsclaw C. M., Schelle M. W., Botyanszki Z., Gilmore S. A., Tully S. E., Niederweis M., Cravatt B. F., Leary J. A., Bertozzi C. R. ( 2012). Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosis. J Biol Chem 287:7990–8000 [View Article][PubMed]
     [Google Scholar]
  151. Seibold G. M., Eikmanns B. J. ( 2007). The glgX gene product of Corynebacterium glutamicum is required for glycogen degradation and for fast adaptation to hyperosmotic stress. Microbiology 153:2212–2220 [View Article][PubMed]
     [Google Scholar]
  152. Seibold G. M., Wurst M., Eikmanns B. J. ( 2009). Roles of maltodextrin and glycogen phosphorylases in maltose utilization and glycogen metabolism in Corynebacterium glutamicum. Microbiology 155:347–358 [View Article][PubMed]
     [Google Scholar]
  153. Simeone R., Bobard A., Lippmann J., Bitter W., Majlessi L., Brosch R., Enninga J. ( 2012). Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog 8:e1002507 [View Article][PubMed]
     [Google Scholar]
  154. Singer M. A., Lindquist S. ( 1998). Thermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose. Trends Biotechnol 16:460–468 [View Article][PubMed]
     [Google Scholar]
  155. Singh P., Cole S. T. ( 2011). Mycobacterium leprae: genes, pseudogenes and genetic diversity. Future Microbiol 6:57–71 [View Article][PubMed]
     [Google Scholar]
  156. Stanley S. A., Cox J. S. ( 2013). Host-pathogen interactions during Mycobacterium tuberculosis infections. Curr Top Microbiol Immunol 374:211–241[PubMed]
     [Google Scholar]
  157. Stanley S. A., Grant S. S., Kawate T., Iwase N., Shimizu M., Wivagg C., Silvis M., Kazyanskaya E., Aquadro J. & other authors ( 2012). Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS Chem Biol 7:1377–1384 [View Article][PubMed]
     [Google Scholar]
  158. Stehr M., Elamin A. A., Singh M. ( 2014). Filling the pipeline - new drugs for an old disease. Curr Top Med Chem 14:110–129 [View Article][PubMed]
     [Google Scholar]
  159. Swarts B. M., Holsclaw C. M., Jewett J. C., Alber M., Fox D. M., Siegrist M. S., Leary J. A., Kalscheuer R., Bertozzi C. R. ( 2012). Probing the mycobacterial trehalome with bioorthogonal chemistry. J Am Chem Soc 134:16123–16126 [View Article][PubMed]
     [Google Scholar]
  160. Tahlan K., Wilson R., Kastrinsky D. B., Arora K., Nair V., Fischer E., Barnes S. W., Walker J. R., Alland D. & other authors ( 2012). SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 56:1797–1809 [View Article][PubMed]
     [Google Scholar]
  161. Takayama K., Wang C., Besra G. S. ( 2005). Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18:81–101 [View Article][PubMed]
     [Google Scholar]
  162. Tiago I., Maranha A., Mendes V., Alarico S., Moynihan P. J., Clarke A. J., Macedo-Ribeiro S., Pereira P. J., Empadinhas N. ( 2012). Genome sequence of Mycobacterium hassiacum DSM 44199, a rare source of heat-stable mycobacterial proteins. J Bacteriol 194:7010–7011 [View Article][PubMed]
     [Google Scholar]
  163. Tropis M., Meniche X., Wolf A., Gebhardt H., Strelkov S., Chami M., Schomburg D., Krämer R., Morbach S., Daffé M. ( 2005). The crucial role of trehalose and structurally related oligosaccharides in the biosynthesis and transfer of mycolic acids in Corynebacterineae. J Biol Chem 280:26573–26585 [View Article][PubMed]
     [Google Scholar]
  164. Tsukamura M., Mizuno S., Toyama H. ( 1983). Mycobacterium pulveris sp. nov., a nonphotochromogenic Mycobacterium with an intermediate growth rate. Int J Syst Bacteriol 33:811–815 [View Article]
     [Google Scholar]
  165. van der Wel N., Hava D., Houben D., Fluitsma D., van Zon M., Pierson J., Brenner M., Peters P. J. ( 2007). M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 129:1287–1298 [View Article][PubMed]
     [Google Scholar]
  166. van der Woude A. D., Sarkar D., Bhatt A., Sparrius M., Raadsen S. A., Boon L., Geurtsen J., van der Sar A. M., Luirink J. & other authors ( 2012). Unexpected link between lipooligosaccharide biosynthesis and surface protein release in Mycobacterium marinum. J Biol Chem 287:20417–20429 [View Article][PubMed]
     [Google Scholar]
  167. Varela C., Rittmann D., Singh A., Krumbach K., Bhatt K., Eggeling L., Besra G. S., Bhatt A. ( 2012). MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria. Chem Biol 19:498–506 [View Article][PubMed]
     [Google Scholar]
  168. Varghese B., Memish Z., Abuljadayel N., Al-Hakeem R., Alrabiah F., Al-Hajoj S. A. ( 2013). Emergence of clinically relevant non-tuberculous mycobacterial infections in Saudi Arabia. PLoS Negl Trop Dis 7:e2234 [View Article][PubMed]
     [Google Scholar]
  169. Verschoor J. A., Baird M. S., Grooten J. ( 2012). Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis. Prog Lipid Res 51:325–339 [View Article][PubMed]
     [Google Scholar]
  170. Villeneuve C., Etienne G., Abadie V., Montrozier H., Bordier C., Laval F., Daffe M., Maridonneau-Parini I., Astarie-Dequeker C. ( 2003). Surface-exposed glycopeptidolipids of Mycobacterium smegmatis specifically inhibit the phagocytosis of mycobacteria by human macrophages. Identification of a novel family of glycopeptidolipids. J Biol Chem 278:51291–51300 [View Article][PubMed]
     [Google Scholar]
  171. Viveiros M., Martins M., Rodrigues L., Machado D., Couto I., Ainsa J., Amaral L. ( 2012). Inhibitors of mycobacterial efflux pumps as potential boosters for anti-tubercular drugs. Expert Rev Anti Infect Ther 10:983–998 [View Article][PubMed]
     [Google Scholar]
  172. Wallace R. J. Jr, Brown B. A., Griffith D. E. ( 1998). Nosocomial outbreaks/pseudo-outbreaks caused by nontuberculous mycobacteria. Annu Rev Microbiol 52:453–490 [View Article][PubMed]
     [Google Scholar]
  173. Wang J., Elchert B., Hui Y., Takemoto J. Y., Bensaci M., Wennergren J., Chang H., Rai R., Chang C. W. ( 2004). Synthesis of trehalose-based compounds and their inhibitory activities against Mycobacterium smegmatis. Bioorg Med Chem 12:6397–6413 [View Article][PubMed]
     [Google Scholar]
  174. Wang H., Edwards M., Falkinham J. O. III, Pruden A. ( 2012). Molecular survey of the occurrence of Legionella spp., Mycobacterium spp., Pseudomonas aeruginosa, and amoeba hosts in two chloraminated drinking water distribution systems. Appl Environ Microbiol 78:6285–6294 [View Article][PubMed]
     [Google Scholar]
  175. Warrier T., Tropis M., Werngren J., Diehl A., Gengenbacher M., Schlegel B., Schade M., Oschkinat H., Daffe M. & other authors ( 2012). Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis. Antimicrob Agents Chemother 56:1735–1743 [View Article][PubMed]
     [Google Scholar]
  176. Webb K. M., DiRuggiero J. ( 2012). Role of Mn2+ and compatible solutes in the radiation resistance of thermophilic bacteria and archaea. Archaea 2012:845756 [View Article][PubMed]
     [Google Scholar]
  177. Welsh K. J., Hunter R. L., Actor J. K. ( 2013). Trehalose 6,6′-dimycolate–a coat to regulate tuberculosis immunopathogenesis. Tuberculosis (Edinb) 93:Suppl.S3–S9 [View Article][PubMed]
     [Google Scholar]
  178. Wiggers H. A. L. ( 1832). Untersuchung über das Mutterkorn, Secale cornutum. Ann Pharmacie 1:129–182 [View Article]
     [Google Scholar]
  179. Wilson R. A., Maughan W. N., Kremer L., Besra G. S., Fütterer K. ( 2004). The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of non-catalytic alpha/beta hydrolases. J Mol Biol 335:519–530 [View Article][PubMed]
     [Google Scholar]
  180. Woodruff P. J., Carlson B. L., Siridechadilok B., Pratt M. R., Senaratne R. H., Mougous J. D., Riley L. W., Williams S. J., Bertozzi C. R. ( 2004). Trehalose is required for growth of Mycobacterium smegmatis. J Biol Chem 279:28835–28843 [View Article][PubMed]
     [Google Scholar]
  181. Yang Y., Kulka K., Montelaro R. C., Reinhart T. A., Sissons J., Aderem A., Ojha A. K. ( 2014). A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis. Cell Host Microbe 15:153–163 [View Article][PubMed]
     [Google Scholar]
  182. Zhang M., Yang Y., Xu Y., Qie Y., Wang J., Zhu B., Wang Q., Jin R., Xu S., Wang H. ( 2007). Trehalose-6-phosphate phosphatase from Mycobacterium tuberculosis induces humoral and cellular immune responses. FEMS Immunol Med Microbiol 49:68–74 [View Article][PubMed]
     [Google Scholar]
  183. Zhang R., Pan Y. T., He S., Lam M., Brayer G. D., Elbein A. D., Withers S. G. ( 2011). Mechanistic analysis of trehalose synthase from Mycobacterium smegmatis. J Biol Chem 286:35601–35609 [View Article][PubMed]
     [Google Scholar]
  184. Zumla A., Nahid P., Cole S. T. ( 2013). Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov 12:388–404 [View Article][PubMed]
     [Google Scholar]
  185. Zumla A. I., Gillespie S. H., Hoelscher M., Philips P. P., Cole S. T., Abubakar I., McHugh T. D., Schito M., Maeurer M., Nunn A. J. ( 2014). New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects. Lancet Infect Dis 14:327–340 [View Article][PubMed]
     [Google Scholar]
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The molecular biology of mycobacterial trehalose in the quest for advanced tuberculosis therapies
Microbiology 160, 1547 (2014); https://doi.org/10.1099/mic.0.075895-0
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