title: The mycobacterial cell envelope-lipids.
abstract: Mycobacterium tuberculosis (Mtb) lipids are indelibly imprinted in just about every key aspect of tuberculosis (TB) basic and translational research. Although the interest in these compounds originally stemmed from their abundance, structural diversity, and antigenicity, continued research in this field has been driven by their important contribution to TB pathogenesis and their interest from the perspective of drug, vaccine, diagnostic, and biomarker development. This article summarizes what is known of the roles of lipids in the physiology and pathogenicity of Mtb and the exciting developments that have occurred in recent years in identifying new lead compounds targeting their biogenesis.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Colorado 80523-1682.
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
mesh_terms: D002462:Cell Membrane / Q000648:ultrastructure; D015195:Drug Design; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity*; D009171:Mycolic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D008563:Membrane Lipids; D009171:Mycolic Acids; D013729:Terpenes
references.citation: Bioorg Med Chem Lett. 2008 Nov 15;18(22):5963-6
references.pmid: 18762421
references.citation: Infect Immun. 2013 Mar;81(3):764-76
references.pmid: 23264051
references.citation: J Bacteriol. 1997 Dec;179(24):7827-33
references.pmid: 9401044
references.citation: Antimicrob Agents Chemother. 2011 Aug;55(8):3889-98
references.pmid: 21628538
references.citation: Eur J Immunol. 2011 Feb;41(2):450-60
references.pmid: 21268014
references.citation: J Immunol Methods. 1994 Dec 28;177(1-2):69-77
references.pmid: 7822839
references.citation: J Biol Chem. 2010 Oct 29;285(44):33577-83
references.pmid: 20801880
references.citation: PLoS One. 2010 Jun 14;5(6):e11108
references.pmid: 20559431
references.citation: J Biol Chem. 2013 Oct 18;288(42):30309-30319
references.pmid: 23986448
references.citation: J Lipid Res. 2005 Mar;46(3):475-83
references.pmid: 15576843
references.citation: Annu Rev Biochem. 1995;64:29-63
references.pmid: 7574484
references.citation: Adv Exp Med Biol. 2013;783:181-97
references.pmid: 23468110
references.citation: Antimicrob Agents Chemother. 2012 Jan;56(1):324-31
references.pmid: 22024828
references.citation: J Biol Chem. 2002 Aug 30;277(35):31335-44
references.pmid: 12068013
references.citation: J Bacteriol. 2008 Aug;190(16):5672-80
references.pmid: 18567661
references.citation: J Biol Chem. 2006 Sep 1;281(35):25143-55
references.pmid: 16803893
references.citation: Science. 2009 May 8;324(5928):801-4
references.pmid: 19299584
references.citation: Anal Biochem. 2009 Feb 1;385(1):120-7
references.pmid: 18992216
references.citation: Microbiology (Reading). 1995 Jul;141 ( Pt 7):1609-20
references.pmid: 7551029
references.citation: Curr Top Med Chem. 2011;11(11):1352-69
references.pmid: 21513496
references.citation: Science. 1994 Jan 14;263(5144):227-30
references.pmid: 8284673
references.citation: Biotechnol Res Int. 2011;2011:274693
references.pmid: 21350659
references.citation: Immunol Rev. 2011 Mar;240(1):252-68
references.pmid: 21349098
references.citation: Jpn J Med Sci Biol. 1970 Oct;23(5):327-33
references.pmid: 4925916
references.citation: Eur J Med Chem. 2012 May;51:1-16
references.pmid: 22421275
references.citation: ACS Chem Biol. 2012 Aug 17;7(8):1377-84
references.pmid: 22577943
references.citation: Cell Microbiol. 2004 Feb;6(2):105-16
references.pmid: 14706097
references.citation: Antimicrob Agents Chemother. 1999 May;43(5):1042-51
references.pmid: 10223912
references.citation: Adv Appl Microbiol. 2009;69:23-78
references.pmid: 19729090
references.citation: Clin Dev Immunol. 2012;2012:981821
references.pmid: 22536277
references.citation: Tuberculosis (Edinb). 2011 Jul;91(4):277-86
references.pmid: 21482481
references.citation: FEMS Microbiol Lett. 1994 Oct 15;123(1-2):11-8
references.pmid: 7988876
references.citation: Cell Microbiol. 2004 Mar;6(3):277-87
references.pmid: 14764111
references.citation: Bioorg Med Chem Lett. 2011 Dec 1;21(23):6973-6
references.pmid: 22024034
references.citation: Nature. 2004 Sep 2;431(7004):84-7
references.pmid: 15343336
references.citation: Front Biosci. 1998 Dec 15;3:D1253-61
references.pmid: 9851911
references.citation: mBio. 2013 Feb 19;4(1):e00472-12
references.pmid: 23422411
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000645
references.pmid: 19876393
references.citation: PLoS Pathog. 2009 Aug;5(8):e1000545
references.pmid: 19680450
references.citation: Tuberculosis (Edinb). 2007 Mar;87(2):78-86
references.pmid: 17030019
references.citation: PLoS One. 2013;8(3):e58378
references.pmid: 23472191
references.citation: Cell Microbiol. 2013 Apr;15(4):660-74
references.pmid: 23121245
references.citation: Infect Immun. 2003 Aug;71(8):4684-90
references.pmid: 12874349
references.citation: Adv Exp Med Biol. 2013;783:199-223
references.pmid: 23468111
references.citation: Nat Commun. 2013;4:2748
references.pmid: 24193546
references.citation: Chem Biol. 2008 Jan;15(1):51-61
references.pmid: 18158259
references.citation: Tuberculosis (Edinb). 2010 Nov;90(6):354-60
references.pmid: 20934382
references.citation: Clin Microbiol Infect. 1996 Feb;2(3):214-222
references.pmid: 11866846
references.citation: Bioorg Med Chem Lett. 2010 Nov 1;20(21):6306-9
references.pmid: 20850304
references.citation: J Clin Microbiol. 2002 Oct;40(10):3782-8
references.pmid: 12354881
references.citation: Antimicrob Agents Chemother. 2008 Mar;52(3):1162-6
references.pmid: 18086849
references.citation: Glycoconj J. 2009 Jul;26(5):589-96
references.pmid: 19052863
references.citation: Curr Pharm Des. 2014;20(27):4357-78
references.pmid: 24245756
references.citation: J Bacteriol. 2007 Apr;189(7):2583-9
references.pmid: 17237171
references.citation: J Biol Chem. 2012 Nov 9;287(46):38434-41
references.pmid: 23002234
references.citation: Eur J Clin Microbiol Infect Dis. 1995 Oct;14(10):883-91
references.pmid: 8605902
references.citation: Mol Microbiol. 1998 Sep;29(6):1449-58
references.pmid: 9781881
references.citation: Lancet Infect Dis. 2013 Apr;13(4):362-72
references.pmid: 23531389
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2510-7
references.pmid: 23776209
references.citation: PLoS One. 2013 Sep 23;8(9):e75245
references.pmid: 24086479
references.citation: Lancet Infect Dis. 2007 May;7(5):328-37
references.pmid: 17448936
references.citation: Chembiochem. 2012 Jan 2;13(1):129-36
references.pmid: 22109989
references.citation: Antimicrob Agents Chemother. 2012 Apr;56(4):1735-43
references.pmid: 22290959
references.citation: Adv Microb Physiol. 1998;39:131-203
references.pmid: 9328647
references.citation: Microbiol Spectr. 2014 Aug;2(4):MGM2-0021-2013
references.pmid: 26104202
references.citation: PLoS One. 2011;6(9):e23870
references.pmid: 21931620
references.citation: Mol Cell. 2000 Apr;5(4):717-27
references.pmid: 10882107
references.citation: ACS Med Chem Lett. 2011 Nov 10;2(11):818-823
references.pmid: 22267981
references.citation: J Exp Med. 1950 Feb;91(2):197-218, pl
references.pmid: 15404225
references.citation: Infect Immun. 2008 Jul;76(7):3027-36
references.pmid: 18443098
references.citation: J Infect Dis. 2005 Jul 1;192(1):98-106
references.pmid: 15942899
references.citation: J Bacteriol. 1996 Jan;178(2):456-61
references.pmid: 8550466
references.citation: J Biol Chem. 2009 Oct 2;284(40):27101-13
references.pmid: 19648652
references.citation: J Biol Chem. 2001 Jun 8;276(23):19845-54
references.pmid: 11279114
references.citation: Xenobiotica. 2010 Mar;40(3):225-34
references.pmid: 20038272
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4548-53
references.pmid: 15767566
references.citation: Infect Immun. 1974 Jan;9(1):150-8
references.pmid: 4271720
references.citation: Nat Chem Biol. 2012 Feb 19;8(4):334-41
references.pmid: 22344175
references.citation: Bioorg Med Chem. 2010 Oct 1;18(19):7121-31
references.pmid: 20800502
references.citation: Curr Med Chem. 2011;18(9):1325-38
references.pmid: 21366531
references.citation: EMBO Mol Med. 2012 Oct;4(10):1032-42
references.pmid: 22987724
references.citation: PLoS Pathog. 2010 Mar 05;6(3):e1000794
references.pmid: 20221442
references.citation: Medchemcomm. 2012 Aug 1;3(8):899-904
references.pmid: 23926455
references.citation: APMIS. 2014 Apr;122(4):268-82
references.pmid: 23919648
references.citation: EMBO Mol Med. 2012 Jan;4(1):27-37
references.pmid: 22147526
references.citation: Nat Med. 2000 Sep;6(9):1043-7
references.pmid: 10973326
references.citation: Transbound Emerg Dis. 2009 Aug;56(6-7):255-68
references.pmid: 19486312
references.citation: J Med Chem. 2012 Apr 26;55(8):3739-55
references.pmid: 22449052
references.citation: Cell. 2005 Dec 2;123(5):861-73
references.pmid: 16325580
references.citation: Future Microbiol. 2013 Jul;8(7):855-75
references.pmid: 23841633
references.citation: Tuberculosis (Edinb). 2011 May;91(3):187-95
references.pmid: 21330212
references.citation: Future Microbiol. 2012 Jul;7(7):823-37
references.pmid: 22827305
references.citation: PLoS One. 2013;8(1):e53162
references.pmid: 23301038
references.citation: Nat Genet. 2013 Feb;45(2):172-9
references.pmid: 23291586
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3963-7
references.pmid: 18316738
references.citation: J Biomol Screen. 2013 Jun;18(5):576-87
references.pmid: 23364516
references.citation: Bioorg Med Chem Lett. 2012 May 1;22(9):3349-53
references.pmid: 22469702
references.citation: ACS Chem Biol. 2011 Aug 19;6(8):819-28
references.pmid: 21595486
references.citation: Anal Biochem. 2012 Feb 1;421(1):240-9
references.pmid: 22107887
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11565-70
references.pmid: 23798446
references.citation: J Biol Chem. 2010 Jun 4;285(23):17380-9
references.pmid: 20375425
references.citation: J Biol Chem. 2005 Jun 3;280(22):21645-52
references.pmid: 15805104
references.citation: Tuberculosis (Edinb). 2008 Nov;88(6):560-5
references.pmid: 18539533
references.citation: Biochem J. 2005 Dec 15;392(Pt 3):615-24
references.pmid: 16092920
references.citation: Microbiology (Reading). 2008 Jul;154(Pt 7):1866-1875
references.pmid: 18599816
references.citation: J Biol Chem. 2002 Oct 11;277(41):38148-58
references.pmid: 12138124
references.citation: J Exp Med. 2009 Dec 21;206(13):2879-88
references.pmid: 20008526
references.citation: mBio. 2013 May 07;4(3):e00222-13
references.pmid: 23653446
references.citation: J Exp Med. 2013 Apr 8;210(4):729-41
references.pmid: 23530121
references.citation: Prog Lipid Res. 1998 Jul-Aug;37(2-3):143-79
references.pmid: 9829124
references.citation: J Biol Chem. 2006 Jan 20;281(3):1313-6
references.pmid: 16326699
references.citation: Mol Microbiol. 2000 May;36(3):630-7
references.pmid: 10844652
references.citation: Cell Microbiol. 2003 Jun;5(6):405-15
references.pmid: 12780778
references.citation: Nature. 2000 Jun 22;405(6789):962-6
references.pmid: 10879539
references.citation: PLoS Med. 2006 Nov;3(11):e466
references.pmid: 17132069
references.citation: Mol Microbiol. 2007 Mar;63(5):1345-59
references.pmid: 17302813
references.citation: Nat Chem Biol. 2013 Aug;9(8):499-506
references.pmid: 23770708
references.citation: Nat Med. 2009 May;15(5):537-44
references.pmid: 19412174
references.citation: Antimicrob Agents Chemother. 1995 Nov;39(11):2484-9
references.pmid: 8585730
references.citation: Eur J Biochem. 1987 Aug 17;167(1):155-60
references.pmid: 3113946
references.citation: Mol Microbiol. 2009 Apr;72(1):85-97
references.pmid: 19220750
references.citation: Bioorg Med Chem Lett. 2006 Sep 15;16(18):4743-7
references.pmid: 16875817
references.citation: Crit Rev Eukaryot Gene Expr. 2012;22(4):289-97
references.pmid: 23272799
references.citation: Biochem J. 1994 Jan 15;297 ( Pt 2):351-7
references.pmid: 8297342
references.citation: Antimicrob Agents Chemother. 2012 Apr;56(4):1797-809
references.pmid: 22252828
references.citation: PLoS Pathog. 2010 Sep 09;6(9):e1001100
references.pmid: 20844580
references.citation: Biochem J. 2003 May 15;372(Pt 1):77-86
references.pmid: 12593673
references.citation: Infect Immun. 1974 Jan;9(1):142-9
references.pmid: 4202886
references.citation: J Gen Microbiol. 1988 Jul;134(7):2049-55
references.pmid: 3149973
references.citation: PLoS Pathog. 2008 Nov;4(11):e1000204
references.pmid: 19002241
references.citation: Annu Rev Microbiol. 2007;61:35-50
references.pmid: 18035606
references.citation: PLoS One. 2013 Apr 17;8(4):e60933
references.pmid: 23613759
references.citation: J Microbiol Methods. 2009 Dec;79(3):358-63
references.pmid: 19857528
references.citation: PLoS One. 2013;8(2):e56980
references.pmid: 23437287
references.citation: PLoS One. 2007 Dec 19;2(12):e1343
references.pmid: 18094751
references.citation: Microbes Infect. 2006 Jan;8(1):183-90
references.pmid: 16182591
references.citation: J Cell Biol. 2002 Aug 5;158(3):421-6
references.pmid: 12147678
references.citation: J Bacteriol. 2004 Aug;186(15):5017-30
references.pmid: 15262939
references.citation: Mol Microbiol. 2010 Mar;75(5):1064-77
references.pmid: 20487298
references.citation: Cell Microbiol. 2014 Feb;16(2):195-213
references.pmid: 24028583
references.citation: J Immunol. 2009 Jun 1;182(11):7030-7
references.pmid: 19454700
references.citation: Microbiology (Reading). 2006 Sep;152(Pt 9):2717-2725
references.pmid: 16946266
references.citation: Eur J Immunol. 2012 Feb;42(2):385-92
references.pmid: 22105536
references.citation: J Biol Chem. 2013 Mar 8;288(10):6788-800
references.pmid: 23306194
references.citation: J Med Microbiol. 2002 Feb;51(2):131-137
references.pmid: 11863264
references.citation: Curr Top Med Chem. 2012;12(7):672-93
references.pmid: 22283812
references.citation: FEMS Microbiol Immunol. 1991 Aug;3(4):201-4
references.pmid: 1931132
references.citation: J Bacteriol. 2011 Oct;193(20):5802-9
references.pmid: 21840972
references.citation: Biochemistry. 1991 Jan 15;30(2):378-88
references.pmid: 1899023
references.citation: Glycobiology. 2013 Aug;23(8):926-34
references.pmid: 23576535
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11554-9
references.pmid: 10500215
references.citation: Mol Microbiol. 2006 Apr;60(2):312-30
references.pmid: 16573683
references.citation: J Lipid Res. 2013 Oct;54(10):2924-32
references.pmid: 23797850