Structural and biological diversity of lipopolysaccharides from Burkholderia pseudomallei and Burkholderia thailandensis.
Burkholderia pseudomallei, the etiological agent of melioidosis, is a facultative intracellular pathogen. As B. pseudomallei is a gram-negative bacterium, its outer membrane contains lipopolysaccharide (LPS) molecules, which have been shown to have low-level immunological activities in vitro. In this study, the biological activities of B. pseudomallei LPS were compared to those of Burkholderia thailandensis LPS, and it was found that both murine and human macrophages produced levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-10 in response to B. pseudomallei LPS that were lower than those in response to B. thailandensis LPS in vitro. In order to elucidate the molecular mechanisms underlying the low-level immunological activities of B. pseudomallei LPS, its lipid A moiety was characterized using mass spectrometry. The major lipid A species identified in B. pseudomallei consists of a biphosphorylated disaccharide backbone, which is modified with 4-amino-4-deoxy-arabinose (Ara4N) at both phosphates and penta-acylated with fatty acids (FA) C(14:0)(3-OH), C(16:0)(3-OH), and either C(14:0) or C(14:0)(2-OH). In contrast, the major lipid A species identified in B. thailandensis was a mixture of tetra- and penta-acylated structures with differing amounts of Ara4N and FA C(14:0)(3-OH). Lipid A species acylated with FA C(14:0)(2-OH) were unique to B. pseudomallei and not found in B. thailandensis. Our data thus indicate that B. pseudomallei synthesizes lipid A species with long-chain FA C(14:0)(2-OH) and Ara4N-modified phosphate groups, allowing it to evade innate immune recognition.
Novem
Vidhya
V
Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
Shui
Guanghou
G
Wang
Dongling
D
Bendt
Anne K
AK
Sim
Siew Hoon
SH
Liu
Yichun
Y
Thong
Tuck Weng
TW
Sivalingam
Suppiah Paramalingam
SP
Ooi
Eng Eong
EE
Wenk
Markus R
MR
Tan
Gladys
G
D000818:Animals; D019117:Burkholderia / Q000737:chemistry* / Q000276:immunology; D016957:Burkholderia pseudomallei / Q000737:chemistry* / Q000276:immunology / Q000472:pathogenicity; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007113:Immunity, Innate; D008050:Lipid A / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014774:Virulence / Q000276:immunology
D016207:Cytokines; D008050:Lipid A; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
Infect Immun. 2007 Sep;75(9):4298-304
17576760
J Med Microbiol. 2004 Dec;53(Pt 12):1177-1182
15585494
Curr Opin Infect Dis. 2004 Apr;17(2):131-6
15021053
Analyst. 2000 Apr;125(4):651-6
10892021
Am J Trop Med Hyg. 2006 Nov;75(5):947-54
17123994
Microbes Infect. 1999 Feb;1(2):157-62
10594980
Microbes Infect. 2003 Oct;5(12):1057-63
14554246
Annu Rev Biochem. 2002;71:635-700
12045108
Trans R Soc Trop Med Hyg. 2006 Jul;100(7):687-92
16343569
Mol Microbiol. 2007 Jan;63(2):379-90
17163980
Infect Immun. 2001 Mar;69(3):1477-82
11179315
Nat Immunol. 2006 Oct;7(10):1066-73
16980981
J Biol Chem. 2001 Nov 16;276(46):43111-21
11535603
J Lipid Res. 2007 Sep;48(9):1976-84
17565170
Rev Infect Dis. 1989 May-Jun;11(3):413-25
2665001
Acta Trop. 2000 Feb 5;74(2-3):159-68
10674645
J Immunol. 2000 Jul 15;165(2):618-22
10878331
Clin Exp Immunol. 2000 Dec;122(3):324-9
11122236
J Clin Microbiol. 2003 Oct;41(10):4812-4
14532228
Microbiol Immunol. 2001;45(4):307-13
11386421
BMC Immunol. 2008 Aug 08;9:46
18691413
J Bacteriol. 2005 Apr;187(7):2448-57
15774888
J Infect Dis. 2007 Oct 1;196(7):1088-92
17763333
PLoS Med. 2007 Jul 31;4(7):e248
17676990
Biochem Cell Biol. 2004 Feb;82(1):71-86
15052329
J Endotoxin Res. 2005;11(2):89-96
15949135
J Biol Chem. 2000 Oct 20;275(42):32940-9
10903325
J Infect Dis. 1989 May;159(5):890-9
2708842
J Clin Invest. 1996 Jan 15;97(2):359-65
8567955
Infect Immun. 1995 Sep;63(9):3348-52
7543882
Clin Infect Dis. 1999 Oct;29(4):813-8
10589895
Ann N Y Acad Sci. 2007 Jan;1096:1-17
17405910
J Immunol. 2002 Apr 15;168(8):4012-7
11937558
Curr Opin Infect Dis. 2009 Apr;22(2):102-8
19276877
Glycobiology. 2005 May;15(5):561-70
15610978
J Clin Microbiol. 2006 Dec;44(12):4601-4
17050819
Emerg Infect Dis. 2005 Sep;11(9):1458-60
16229782
Clin Microbiol Rev. 2005 Apr;18(2):383-416
15831829
Infect Immun. 1997 Oct;65(10):4319-21
9317042
Infect Immun. 2005 May;73(5):2940-50
15845500
J Endotoxin Res. 2001;7(1):57-62
11521084
Chem Immunol. 2000;74:5-24
10608079
FASEB J. 1994 Feb;8(2):217-25
8119492
Clin Microbiol Rev. 1991 Jan;4(1):52-60
2004347
Postgrad Med J. 2002 Apr;78(918):216-24
11930024
Science. 1997 Apr 11;276(5310):250-3
9092473
Nat Rev Microbiol. 2005 Jan;3(1):36-46
15608698
Infect Immun. 1997 Sep;65(9):3648-53
9284132
Infect Immun. 2004 Sep;72(9):5340-8
15322031
Bol Asoc Med P R. 2003 Nov-Dec;95(6):17-20
15449787
Chemistry. 2003 Apr 4;9(7):1542-8
12658652
FEMS Microbiol Lett. 1996 Mar 15;137(1):79-83
8935661
Pharm Res. 2008 Aug;25(8):1751-61
18493843
Carbohydr Res. 2003 Nov 14;338(23):2431-47
14670707
Infect Immun. 1999 Mar;67(3):1505-7
10024601
Infect Immun. 1996 Mar;64(3):782-90
8641782
Trends Microbiol. 1999 Apr;7(4):138-40
10217823
J Biol Chem. 1971 May 10;246(9):3042-9
4928897
Appl Environ Microbiol. 2007 Mar;73(6):1803-8
17261511