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Volume 167, Issue 3

Roles for phthiocerol dimycocerosate lipids in pathogenesis Open Access

Abstract

The success of as a pathogen is well established: tuberculosis is the leading cause of death by a single infectious agent worldwide. The threat of multi- and extensively drug-resistant bacteria has renewed global concerns about this pathogen and understanding its virulence strategies will be essential in the fight against tuberculosis. The current review will focus on phthiocerol dimycocerosates (PDIMs), a long-known and well-studied group of complex lipids found in the cell envelope. Numerous studies show a role for PDIMs in several key steps of pathogenesis, with recent studies highlighting its involvement in bacterial virulence, in association with the ESX-1 secretion system. Yet, the mechanisms by which PDIMs help to control macrophage phagocytosis, inhibit phagosome acidification and modulate host innate immunity, remain to be fully elucidated.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): ESX-1 , mycobacteria outer membrane , Mycobacterium tuberculosis and PDIM
Funding
This study was supported by the:
  • CIHR Skin Research Training Centre (CA) (Award PJ-148646)
    • Principle Award Recipient: YossefAv-Gay
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-02-25
2024-04-27
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References

  1. Comas I, Coscolla M, Luo T, Borrell S, Holt KE et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet 2013
     [Google Scholar]
  2. WHO WHO | Global Tuberculosis Report 2019 World Health Organization; 2020
     [Google Scholar]
  3. Galagan JE. Genomic insights into tuberculosis. Nat Rev Genet 2014; 15:307–320 [View Article][PubMed]
     [Google Scholar]
  4. Fabre M, Koeck JL, Le Flèche P, Simon F, Hervé V et al. High genetic diversity revealed by variable-number tandem repeat genotyping and analysis of hsp65 gene polymorphism in a large collection of “Mycobacterium canettii” strains indicates that the M. tuberculosis complex is a recently emerged clone of "M. can. J Clin Microbiol. 2004
     [Google Scholar]
  5. Boritsch EC, Supply P, Honoré N, Seemann T, Seeman T, Stinear TP et al. A glimpse into the past and predictions for the future: the molecular evolution of the tuberculosis agent. Mol Microbiol 2014; 93:835–852 [View Article][PubMed]
     [Google Scholar]
  6. Jackson M. The mycobacterial cell envelope-lipids. Cold Spring Harb Perspect Med 2014
     [Google Scholar]
  7. Daffé M, Crick DC, Jackson M. Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids. Molecular Genetics of Mycobacteria 2015
     [Google Scholar]
  8. Dulberger CL, Rubin EJ, Boutte CC. The mycobacterial cell envelope — a moving target. Nat Rev Microbiol 2020; 18:47–59 [View Article]
     [Google Scholar]
  9. Hoffmann C, Leis A, Niederweis M, Plitzko JM, Engelhardt H. Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc Natl Acad Sci U S A 2008
     [Google Scholar]
  10. Zuber B, Chami M, Houssin C, Dubochet J, Griffiths G et al. Direct visualization of the outer membrane of mycobacteria and corynebacteria in their native state. J Bacteriol 2008
     [Google Scholar]
  11. Vincent AT, Nyongesa S, Morneau I, Reed MB, Tocheva EI et al. The mycobacterial cell envelope: a relict from the past or the result of recent evolution?. Front Microbiol 2018; 9: [View Article]
     [Google Scholar]
  12. Jain P, Hsu T, Arai M, Biermann K, Thaler DS et al. Specialized transduction designed for precise high-throughput unmarked deletions in Mycobacterium tuberculosis . mBio 2014; 5: [View Article]
     [Google Scholar]
  13. Liu J, Rosenberg EY, Nikaido H. Fluidity of the lipid domain of cell wall from Mycobacterium chelonae . Proc Natl Acad Sci U S A 1995
     [Google Scholar]
  14. Hunter RL, Hwang S-A, Jagannath C, Actor JK. Cord factor as an invisibility cloak? A hypothesis for asymptomatic TB persistence. Tuberculosis 2016; 101:S2–S8 [View Article]
     [Google Scholar]
  15. Queiroz A, Riley LW. Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response. Rev Soc Bras Med Trop 2017; 50:9–18 [View Article][PubMed]
     [Google Scholar]
  16. Onwueme KC, Vos CJ, Zurita J, Ferreras JA, Quadri LEN. The dimycocerosate ester polyketide virulence factors of mycobacteria. Prog Lipid Res 2005; 44:259–302 [View Article][PubMed]
     [Google Scholar]
  17. Guenin-Macé L, Siméone R, Demangel C. Lipids of pathogenic mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis 2009
     [Google Scholar]
  18. Jankute M, Grover S, Birch HL, Besra GS. Genetics of mycobacterial arabinogalactan and lipoarabinomannan assembly. Microbiol Spectr 2014; 2: [View Article]
     [Google Scholar]
  19. Kalscheuer R, Palacios A, Anso I, Cifuente J, Anguita J et al. The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochemical Journal 2019; 476:1995–2016 [View Article]
     [Google Scholar]
  20. Briken V, Porcelli SA, Besra GS, Kremer L. Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol 2004; 53:391–403 [View Article][PubMed]
     [Google Scholar]
  21. Astarie-Dequeker C, Le Guyader L, Malaga W, Seaphanh F-K, Chalut C et al. Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage invasion by inducing changes in the organization of plasma membrane lipids. PLoS Pathog 2009; 5:e1000289 [View Article]
     [Google Scholar]
  22. Quigley J, Hughitt VK, Velikovsky CA, Mariuzza RA, El-Sayed NM et al. The cell wall lipid PDIM contributes to phagosomal escape and host cell exit of Mycobacterium tuberculosis . MBio 2017; 8: [View Article]
     [Google Scholar]
  23. Singh A, Crossman DK, Mai D, Guidry L, Voskuil MI et al. Mycobacterium tuberculosis WhiB3 Maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response. PLoS Pathog 2009; 5:e1000545 [View Article]
     [Google Scholar]
  24. Augenstreich J, Arbues A, Simeone R, Haanappel E, Wegener A et al. ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cell Microbiol. 2017
     [Google Scholar]
  25. Barczak AK, Avraham R, Singh S, Luo SS, Zhang WR et al. Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence. PLoS Pathog 2017; 13:e1006363 [View Article]
     [Google Scholar]
  26. Trivedi OA, Arora P, Sridharan V, Tickoo R, Mohanty D et al. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 2004
     [Google Scholar]
  27. Trivedi OA, Arora P, Vats A, Ansari MZ, Tickoo R et al. Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol Cell. 2005
     [Google Scholar]
  28. Siméone R, Constant P, Guilhot C, Daffé M, Chalut C. Identification of the missing trans-acting enoyl reductase required for phthiocerol dimycocerosate and phenolglycolipid biosynthesis in Mycobacterium tuberculosis . J Bacteriol. 2007
     [Google Scholar]
  29. Chavadi SS, Edupuganti UR, Vergnolle O, Fatima I, Singh SM et al. Inactivation of tesA reduces cell wall lipid production and increases drug susceptibility in mycobacteria. J Biol Chem 2011
     [Google Scholar]
  30. Azad AK, Sirakova TD, Rogers LM, Kolattukudy PE. Targeted replacement of the mycocerosic acid synthase gene in Mycobacterium bovis BCG produces a mutant that lacks mycosides. Proc Natl Acad Sci U S A 1996
     [Google Scholar]
  31. Fitzmaurice AM, Kolattukudy PE. An acyl-CoA synthase (acoas) gene adjacent to the mycocerosic acid synthase (mas) locus is necessary for mycocerosyl lipid synthesis in Mycobacterium tuberculosis var. bovis BCG. J Biol Chem. 1998
     [Google Scholar]
  32. Pérez E, Constant P, Laval F, Lemassu A, Lanéelle MA et al. Molecular dissection of the role of two methyltransferases in the biosynthesis of phenolglycolipids and phthiocerol dimycoserosate in the Mycobacterium tuberculosis complex. J Biol Chem 2004
     [Google Scholar]
  33. Onwueme KC, Vos CJ, Zurita J, Soll CE, Quadri LEN. Identification of phthiodiolone ketoreductase, an enzyme required for production of mycobacterial diacyl phthiocerol virulence factors. J Bacteriol 2005
     [Google Scholar]
  34. Jain M, Cox JS. Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis . PLoS Pathog 2005; 1:e2 [View Article]
     [Google Scholar]
  35. Sulzenbacher G, Canaan S, Bordat Y, Neyrolles O, Stadthagen G et al. LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis . Embo J 2006
     [Google Scholar]
  36. Cohen SB, Gern BH, Delahaye JL, Adams KN, Plumlee CR et al. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe 2018; 24:439–446 [View Article][PubMed]
     [Google Scholar]
  37. Bach H, Papavinasasundaram KG, Wong D, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe 2008; 3:316–322 [View Article][PubMed]
     [Google Scholar]
  38. Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H +-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A 2011
     [Google Scholar]
  39. Mwandumba HC, Russell DG, Nyirenda MH, Anderson J, White SA et al. Mycobacterium tuberculosis resides in Nonacidified vacuoles in Endocytically competent alveolar macrophages from patients with tuberculosis and HIV infection. J Immunol. 2004
     [Google Scholar]
  40. Poirier V, Av-Gay Y. Intracellular growth of bacterial pathogens: the role of secreted effector proteins in the control of phagocytosed microorganisms. Microbiol Spectr 2015; 3: [View Article]
     [Google Scholar]
  41. Sundaramurthy V, Korf H, Singla A, Scherr N, Nguyen L et al. Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes in vivo . Microbes Infect 2017
     [Google Scholar]
  42. Srivastava S, Ernst JD, Desvignes L. Beyond macrophages: the diversity of mononuclear cells in tuberculosis. Immunol Rev. 2014
     [Google Scholar]
  43. Srivastava S, Grace PS, Ernst JD. Antigen export reduces antigen presentation and limits T cell control of M. tuberculosis . Cell Host Microbe 2016; 19:44–54 [View Article][PubMed]
     [Google Scholar]
  44. Poirier V, Bach H, Av-Gay Y. Mycobacterium tuberculosis promotes anti-apoptotic activity of the macrophage by PtpA protein-dependent dephosphorylation of host GSK3α. J Biol Chem 2014
     [Google Scholar]
  45. Behar SM, Martin CJ, Booty MG, Nishimura T, Zhao X et al. Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis . Mucosal Immunol 2011; 4:279–287 [View Article][PubMed]
     [Google Scholar]
  46. Gengenbacher M, Kaufmann SHE. Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 2012; 36:514–532 [View Article][PubMed]
     [Google Scholar]
  47. Camacho LR, Ensergueix D, Perez E, Gicquel B, Guilhot C. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol Microbiol. 1999
     [Google Scholar]
  48. Camacho LR, Constant P, Raynaud C, Lanéelle MA, Triccas JA et al. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J Biol Chem 2001
     [Google Scholar]
  49. Murry JP, Pandey AK, Sassetti CM, Rubin EJ. Phthiocerol dimycocerosate transport is required for resisting interferon-γ-independent immunity. J Infect Dis 2009
     [Google Scholar]
  50. Cox JS, Chen B, McNeil M, Jacobs WR. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature 1999; 402:79–83 [View Article][PubMed]
     [Google Scholar]
  51. Rousseau C, Winter N, Privert E, Bordat Y, Neyrolles O et al. Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection. Cell Microbiol. 2004
     [Google Scholar]
  52. Kirksey MA, Tischler AD, Siméone R, Hisert KB, Uplekar S et al. Spontaneous phthiocerol dimycocerosate-deficient variants of Mycobacterium tuberculosis are susceptible to gamma interferon-mediated immunity. Infect Immun. 2011
     [Google Scholar]
  53. Day TA, Mittler JE, Nixon MR, Thompson C, Miner MD et al. Mycobacterium tuberculosis strains lacking surface lipid phthiocerol dimycocerosate are susceptible to killing by an early innate host response. Infect Immun 2014
     [Google Scholar]
  54. Aguilo N, Uranga S, Marinova D, Monzon M, Badiola J et al. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice. Tuberculosis 2016; 96:71–74 [View Article]
     [Google Scholar]
  55. Soetaert K, Rens C, Wang XM, De Bruyn J, Lanéelle MA et al. Increased vancomycin susceptibility in mycobacteria: a new approach to identify synergistic activity against multidrug-resistant mycobacteria. Antimicrob Agents Chemother. 2015
     [Google Scholar]
  56. Mohandas P, Budell WC, Mueller E, Au A, Bythrow GV et al. Pleiotropic consequences of gene knockouts in the phthiocerol dimycocerosate and phenolic glycolipid biosynthetic gene cluster of the opportunistic human pathogen Mycobacterium marinum . FEMS Microbiol Lett 2016; 363:fnw016 [View Article]
     [Google Scholar]
  57. Bisson GP, Mehaffy C, Broeckling C, Prenni J, Rifat D et al. Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by Rifampin-resistant, rpoB mutant Mycobacterium tuberculosis . J Bacteriol 2012
     [Google Scholar]
  58. Howard NC, Marin ND, Ahmed M, Rosa BA, Martin J et al. Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation reprograms macrophage metabolism through cell wall lipid changes. Nature Microbiology 2018; 3:1099–1108 [View Article]
     [Google Scholar]
  59. Han S, Mallampalli RK. The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc 2015; 12:765–774 [View Article]
     [Google Scholar]
  60. Wang Z, Schwab U, Rhoades E, Chess PR, Russell DG et al. Peripheral cell wall lipids of Mycobacterium tuberculosis are inhibitory to surfactant function. Tuberculosis 2008; 88:178–186 [View Article]
     [Google Scholar]
  61. Chimote G, Banerjee R. Lung surfactant dysfunction in tuberculosis: effect of mycobacterial tubercular lipids on dipalmitoylphosphatidylcholine surface activity. Colloids and Surfaces B: Biointerfaces 2005; 45:215–223 [View Article]
     [Google Scholar]
  62. Schwab U, Rohde KH, Wang Z, Chess PR, Notter RH et al. Transcriptional responses of Mycobacterium tuberculosis to lung surfactant. Microb Pathog. 2009
     [Google Scholar]
  63. Cambier CJ, Takaki KK, Larson RP, Hernandez RE, Tobin DM et al. Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature 2014; 505:218–222 [View Article]
     [Google Scholar]
  64. Kawasaki T, Kawai T. Toll-Like receptor signaling pathways. Front Immunol 2014; 5: [View Article]
     [Google Scholar]
  65. Huang L, Nazarova EV, Tan S, Liu Y, Russell DG. Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. J Exp Med 2018; 215:1135–1152 [View Article][PubMed]
     [Google Scholar]
  66. Rothchild AC, Olson GS, Nemeth J, Amon LM, Mai D et al. Alveolar macrophages up-regulate a non-classical innate response to Mycobacterium tuberculosis infection in vivo . bioRxiv 2019
     [Google Scholar]
  67. Ernst JD. Macrophage receptors for Mycobacterium tuberculosis . Infect Immun 1998; 66:1277–1281 [View Article][PubMed]
     [Google Scholar]
  68. Queval CJ, Brosch R, Simeone R. The macrophage: a disputed fortress in the battle against Mycobacterium tuberculosis . Front Microbiol 2017; 8: [View Article]
     [Google Scholar]
  69. Augenstreich J, Haanappel E, Ferré G, Czaplicki G, Jolibois F et al. The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages. Proc Natl Acad Sci U S A 2019
     [Google Scholar]
  70. Augenstreich J, Haanappel E, Sayes F, Simeone R, Guillet V et al. Phthiocerol dimycocerosates from Mycobacterium tuberculosis increase the membrane activity of bacterial effectors and host receptors. Front Cell Infect Microbiol 2020; 10: [View Article]
     [Google Scholar]
  71. Simeone R, Majlessi L, Enninga J, Brosch R. Perspectives on mycobacterial vacuole-to-cytosol translocation: the importance of cytosolic access. Cell Microbiol. 2016
     [Google Scholar]
  72. Duan L, Yi M, Chen J, Li S, Chen W. Mycobacterium tuberculosis EIS gene inhibits macrophage autophagy through up-regulation of IL-10 by increasing the acetylation of histone H3. Biochem Biophys Res Commun 2016
     [Google Scholar]
  73. Lam A, Prabhu R, Gross CM, Riesenberg LA, Singh V et al. Role of apoptosis and autophagy in tuberculosis. Am J Physiol Lung Cell Mol Physiol 2017; 313:L218–L229 [View Article][PubMed]
     [Google Scholar]
  74. Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 2005; 73:1907–1916 [View Article][PubMed]
     [Google Scholar]
  75. Lerner TR, Queval CJ, Fearns A, Repnik U, Griffiths G et al. Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells. BMC Biol 2018; 16: [View Article]
     [Google Scholar]
  76. Peyron P, Vaubourgeix J, Poquet Y, Levillain F, Botanch C et al. Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog 2008; 4:e1000204 [View Article]
     [Google Scholar]
  77. Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci U S A 2008
     [Google Scholar]
  78. Kapoor N, Pawar S, Sirakova TD, Deb C, Warren WL et al. Human Granuloma In Vitro Model, for TB Dormancy and Resuscitation. PLoS One 2013; 8:e53657 [View Article]
     [Google Scholar]
  79. Guirado E, Mbawuike U, Keiser TL, Arcos J, Azad AK et al. Characterization of host and microbial determinants in individuals with latent tuberculosis infection using a human granuloma model. MBio 2015; 6: [View Article]
     [Google Scholar]
  80. Santucci P, Bouzid F, Smichi N, Poncin I, Kremer L et al. Experimental models of foamy macrophages and approaches for dissecting the mechanisms of lipid accumulation and consumption during dormancy and reactivation of tuberculosis. Front Cell Infect Microbiol 2016; 6: [View Article]
     [Google Scholar]
  81. Geisel RE, Sakamoto K, Russell DG, Rhoades ER. In vivo activity of released cell wall lipids of Mycobacterium bovis Bacillus Calmette-Guérin is due principally to trehalose mycolates. J Immunol. 2005
     [Google Scholar]
  82. Hunter RL, Olsen MR, Jagannath C, Actor JK. Multiple roles of cord factor in the pathogenesis of primary, secondary, and cavitary tuberculosis, including a revised description of the pathology of secondary disease. Ann Clin Lab Sci 2006; 36:371-86[PubMed]
     [Google Scholar]
  83. Hunter RL, Olsen M, Jagannath C, Actor JK. Trehalose 6,6′-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am J Pathol. 2006
     [Google Scholar]
  84. Kim MJ, Wainwright HC, Locketz M, Bekker LG, Walther GB et al. Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism. EMBO Mol Med 2010
     [Google Scholar]
  85. Kondo E, Kanai K. Accumulation of cholesterol esters in macrophages incubated with mycobacteria in vitro. Japanese. J Med Sci Biol. 1976
     [Google Scholar]
  86. Griffin JE, Pandey AK, Gilmore SA, Mizrahi V, McKinney JD et al. Cholesterol catabolism by Mycobacterium tuberculosis requires transcriptional and metabolic adaptations. Chem Biol 2012
     [Google Scholar]
  87. Yang X, Nesbitt NM, Dubnau E, Smith I, Sampson NS. Cholesterol metabolism increases the metabolic pool of propionate in Mycobacterium tuberculosis . Biochemistry 2009; 48:3819–3821 [View Article][PubMed]
     [Google Scholar]
  88. Van Der Geize R, Yam K, Heuser T, Wilbrink MH, Hara H et al. A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. Proc Natl Acad Sci U S A 2007
     [Google Scholar]
  89. Wilburn KM, Fieweger RA, VanderVen BC. Cholesterol and fatty acids grease the wheels of Mycobacterium tuberculosis pathogenesis. Pathog Dis 2018; 76: [View Article]
     [Google Scholar]
  90. Muñoz-Elías EJ, Upton AM, Cherian J, McKinney JD. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol 2006
     [Google Scholar]
  91. Savvi S, Warner DF, Kana BD, McKinney JD, Mizrahi V et al. Functional characterization of a vitamin B12-dependent methylmalonyl pathway in Mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids. J Bacteriol 2008; 190:3886–3895 [View Article][PubMed]
     [Google Scholar]
  92. Rainwater DL, Kolattukudy PE. Synthesis of mycocerosic acids from methylmalonyl coenzyme A by cell-free extracts of Mycobacterium tuberculosis var. bovis BCG. J Biol Chem 1983
     [Google Scholar]
  93. Jackson M, Stadthagen G, Gicquel B. Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: Biosynthesis, transport, regulation and biological activities. Tuberculosis 2007; 87:78–86 [View Article]
     [Google Scholar]
  94. Jain M, Petzold CJ, Schelle MW, Leavell MD, Mougous JD et al. Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling. Proc Natl Acad Sci U S A 2007
     [Google Scholar]
  95. Pisu D, Huang L, Grenier JK, Russell DG. Dual RNA-Seq of Mtb-Infected Macrophages In Vivo Reveals Ontologically Distinct Host-Pathogen Interactions. Cell Rep 2020; 30:335–350 [View Article][PubMed]
     [Google Scholar]
  96. Rohde KH, Abramovitch RB, Russell DG. Mycobacterium tuberculosis invasion of macrophages: linking bacterial gene expression to environmental cues. Cell Host Microbe 2007; 2:352–364 [View Article][PubMed]
     [Google Scholar]
  97. Pérez J, Garcia R, Bach H, de Waard JH, Jacobs WR et al. Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. Biochem Biophys Res Commun 2006
     [Google Scholar]
  98. Gupta M, Sajid A, Arora G, Tandon V, Singh Y. Forkhead-associated domain-containing protein Rv0019c and polyketide-associated protein PapA5, from substrates of serine/threonine protein kinase PknB to interacting proteins of Mycobacterium tuberculosis . J Biol Chem. 2009
     [Google Scholar]
  99. Gómez-Velasco A, Bach H, Rana AK, Cox LR, Bhatt A et al. Disruption of the serine/threonine protein kinase H affects phthiocerol dimycocerosates synthesis in Mycobacterium tuberculosis . Microbiol 2013
     [Google Scholar]
  100. Singh P, Sinha R, Tyagi G, Sharma NK, Saini NK et al. PDIM and SL1 accumulation in Mycobacterium tuberculosis is associated with mce4A expression. Gene 2018; 642:178–187 [View Article][PubMed]
     [Google Scholar]
  101. Abdallah AM, Gey van Pittius NC, DiGiuseppe Champion PA, Cox J, Luirink J et al. Type VII secretion - Mycobacteria show the way. Nat Rev Microbiol. 2007
     [Google Scholar]
  102. van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M et al. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 2007; 129:1287–1298 [View Article][PubMed]
     [Google Scholar]
  103. Houben D, Demangel C, van Ingen J, Perez J, Baldeón L et al. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria. Cell Microbiol 2012
     [Google Scholar]
  104. Watson RO, Bell SL, MacDuff DA, Kimmey JM, Diner EJ et al. The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy. Cell Host Microbe 2015; 17:811–819 [View Article][PubMed]
     [Google Scholar]
  105. Blasco B, Chen JM, Hartkoorn R, Sala C, Uplekar S et al. Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog 2012; 8:e1002621 [View Article]
     [Google Scholar]
  106. Gordon BRG, Li Y, Wang L, Sintsova A, Van Bakel H et al. Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis . Proc Natl Acad Sci U S A 2010
     [Google Scholar]
  107. Raman S, Puyang X, Cheng TY, Young DC, Moody DB et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. . J Bacteriol. 2006
     [Google Scholar]
  108. Joshi SA, Ball DA, Sun MG, Carlsson F, Watkins BY et al. EccA1, a component of the Mycobacterium marinum ESX-1 protein virulence factor secretion pathway, regulates mycolic acid lipid synthesis. Chem Biol. 2012
     [Google Scholar]
  109. Carlsson F, Joshi SA, Rangell L, Brown EJ. Polar localization of virulence-related Esx-1 secretion in mycobacteria. PLoS Pathog 2009; 5:e1000285 [View Article]
     [Google Scholar]
  110. Bosserman RE, Champion PA. Esx systems and the mycobacterial cell envelope: What’s the connection?. J Bacteriol 2017; 199: [View Article]
     [Google Scholar]
  111. Domenech P, Reed MB. Rapid and spontaneous loss of phthiocerol dimycocerosate (PDIM) from Mycobacterium tuberculosis grown in vitro: implications for virulence studies. Microbiology 2009; 155:3532–3543 [View Article]
     [Google Scholar]
  112. Giovannini D, Cappelli G, Jiang L, Castilletti C, Colone A et al. A new Mycobacterium tuberculosis smooth colony reduces growth inside human macrophages and represses PDIM Operon gene expression. Does an heterogeneous population exist in intracellular mycobacteria?. Microb Pathog. 2012
     [Google Scholar]
  113. De Majumdar S, Sikri K, Ghosh P, Jaisinghani N, Nandi M et al. Genome analysis identifies a spontaneous nonsense mutation in ppsD leading to attenuation of virulence in laboratory-manipulated Mycobacterium tuberculosis . BMC Genomics 2019; 20: [View Article]
     [Google Scholar]
  114. Goude R, Parish T. Electroporation of mycobacteria. Methods Mol Biol 2008 [View Article]
     [Google Scholar]
  115. Calmette A. Preventive vaccination against tuberculosis with BCG. J R Soc Med 1931
     [Google Scholar]
  116. Flentie KN, Stallings CL, Turk J, Minnaard AJ, Hsu F-F. Characterization of phthiocerol and phthiodiolone dimycocerosate esters of M. tuberculosis by multiple-stage linear ion-trap MS. J Lipid Res 2016; 57:142–155 [View Article][PubMed]
     [Google Scholar]
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Roles for phthiocerol dimycocerosate lipids in Mycobacterium tuberculosis pathogenesis
Microbiology 167, 001042 (2021); https://doi.org/10.1099/mic.0.001042
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