Brucella abortus ornithine lipids are dispensable outer membrane components devoid of a marked pathogen-associated molecular pattern.
The brucellae are α-Proteobacteria facultative intracellular parasites that cause an important zoonosis. These bacteria escape early detection by innate immunity, an ability associated to the absence of marked pathogen-associated molecular patterns in the cell envelope lipopolysaccharide, lipoproteins and flagellin. We show here that, in contrast to the outer membrane ornithine lipids (OL) of other Gram negative bacteria, Brucella abortus OL lack a marked pathogen-associated molecular pattern activity. We identified two OL genes (olsB and olsA) and by generating the corresponding mutants found that olsB deficient B. abortus did not synthesize OL or their lyso-OL precursors. Liposomes constructed with B. abortus OL did not trigger IL-6 or TNF-α release by macrophages whereas those constructed with Bordetella pertussis OL and the olsB mutant lipids as carriers were highly active. The OL deficiency in the olsB mutant did not promote proinflammatory responses or generated attenuation in mice. In addition, OL deficiency did not increase sensitivity to polymyxins, normal serum or complement consumption, or alter the permeability to antibiotics and dyes. Taken together, these observations indicate that OL have become dispensable in the extant brucellae and are consistent within the trend observed in α-Proteobacteria animal pathogens to reduce and eventually eliminate the envelope components susceptible of recognition by innate immunity.
Departamento de Microbiología y Parasitología, Universidad de Navarra, Pamplona, Spain.
Leyre
L
Palacios-Chaves
Raquel
R
Conde-Álvarez
Yolanda
Y
Gil-Ramírez
Amaia
A
Zúñiga-Ripa
Elías
E
Barquero-Calvo
Carlos
C
Chacón-Díaz
Esteban
E
Chaves-Olarte
Vilma
V
Arce-Gorvel
Jean-Pierre
JP
Gorvel
Edgardo
E
Moreno
María-Jesús
MJ
de Miguel
María-Jesús
MJ
Grilló
Ignacio
I
Moriyón
Maite
M
Iriarte
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002003:Brucella abortus / Q000276:immunology* / Q000472:pathogenicity; D002462:Cell Membrane / Q000276:immunology*; D057131:Immune Evasion; D007113:Immunity, Innate; D008055:Lipids / Q000276:immunology*; D008563:Membrane Lipids / Q000276:immunology; D051379:Mice; D009952:Ornithine / Q000031:analogs & derivatives* / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D008055:Lipids; D008563:Membrane Lipids; C051524:ornithine containing aminolipid; D009952:Ornithine
Eur J Biochem. 1973 Apr;34(2):333-44
4351160
PLoS Biol. 2004 Mar;2(3):E69
15024419
Infect Immun. 1989 Jul;57(7):2086-91
2499544
Curr Opin Microbiol. 2006 Feb;9(1):95-101
16406779
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1944-9
19661481
Lipids Health Dis. 2010 Feb 01;9:12
20122166
FEBS Lett. 1974 Aug 1;43(3):257-60
4213476
Vaccine. 2006 Apr 5;24(15):2910-6
16439039
FEMS Microbiol Lett. 1991 Oct 1;67(2):127-9
1778427
J Bacteriol. 2006 Apr;188(8):2761-73
16585737
DNA Cell Biol. 1997 Jun;16(6):691-701
9212163
PLoS One. 2009 Jun 16;4(6):e5893
19529776
J Bacteriol. 2006 Mar;188(5):1929-34
16484204
Mol Plant Microbe Interact. 2003 Jul;16(7):567-79
12848422
Can J Biochem Physiol. 1959 Aug;37(8):911-7
13671378
J Bacteriol. 2005 Aug;187(16):5631-9
16077108
PLoS One. 2008 Jul 23;3(7):e2760
18648644
FEBS J. 2005 Dec;272(24):6354-64
16336272
Cell Microbiol. 2003 Nov;5(11):809-20
14531896
Biochim Biophys Acta. 2006 Sep;1758(9):1513-22
16854372
PLoS One. 2007 Jul 18;2(7):e631
17637846
J Bacteriol. 1993 Aug;175(16):5273-5
8349567
Infect Immun. 1991 Aug;59(8):2560-6
1906840
FEMS Immunol Med Microbiol. 1999 Jan;23(1):67-73
10030549
Mol Plant Microbe Interact. 2005 Nov;18(11):1175-85
16353552
Infect Immun. 2000 Jun;68(6):3210-8
10816465
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9247-52
15956202
J Bacteriol. 1998 Mar;180(6):1425-30
9515909
Appl Environ Microbiol. 2007 Feb;73(4):1375-9
17172460
Infect Immun. 2003 Jun;71(6):3261-71
12761107
Eur J Biochem. 1985 Mar 1;147(2):367-70
3971986
Infect Immun. 1995 Aug;63(8):3054-61
7622230
Dev Biol Stand. 1985;61:249-54
2872110
Prog Lipid Res. 2010 Jan;49(1):46-60
19703488
Mol Microbiol. 2004 Sep;53(6):1757-70
15341653
Infect Immun. 1993 Sep;61(9):3775-84
8359899
J Bacteriol. 1982 Nov;152(2):822-8
6813315
FEMS Immunol Med Microbiol. 2000 Jul;28(3):197-203
10865171
J Bacteriol. 1984 Aug;159(2):776-9
6746578
Microbiol Immunol. 1997;41(2):101-6
9087952
Infect Immun. 1987 Mar;55(3):609-15
3818086
Bacteriol Rev. 1958 Jun;22(2):81-98
13546130
Arch Microbiol. 1977 Jul 26;114(1):87-9
199125
Microbiol Rev. 1985 Mar;49(1):1-32
2580220
Microb Pathog. 2009 Dec;47(6):299-304
19747534
J Bacteriol. 1996 Oct;178(20):5867-76
8830680
FEMS Immunol Med Microbiol. 2000 Jul;28(3):205-9
10865172
J Bacteriol. 1990 Jul;172(7):3569-76
2113907
Genome Res. 2004 Oct;14(10B):2201-6
15489343
J Biol Chem. 2004 May 14;279(20):21046-54
14766898
Cell Microbiol. 2006 Aug;8(8):1322-35
16882035
PLoS Genet. 2007 Jan 19;3(1):e14
17238289
Mol Microbiol. 2002 Aug;45(3):721-33
12139618