Borrelia burgdorferi small lipoprotein Lp6.6 is a member of multiple protein complexes in the outer membrane and facilitates pathogen transmission from ticks to mice.
Borrelia burgdorferi lipoprotein Lp6.6 is a differentially produced spirochete antigen. An assessment of lp6.6 expression covering representative stages of the infectious cycle of spirochetes demonstrates that the gene is solely expressed during pathogen persistence in ticks. Deletion of lp6.6 in infectious B. burgdorferi did not influence in vitro growth, or its ability to persist and induce inflammation in mice, migrate to larval or nymphal ticks or survive through the larval-nymphal molt. However, Lp6.6-deficient spirochetes displayed significant impairment in their ability to transmit from infected ticks to naïve mice, which was restored upon genetic complementation of the mutant with a wild-type copy of lp6.6, establishing that Lp6.6 plays a role in pathogen transmission from ticks to mammals. Lp6.6 is a subsurface, yet highly abundant, outer membrane antigen. Two-dimensional blue native/SDS-PAGE coupled with liquid chromatography-mass spectrometry (LC-MS/MS) analysis and protein cross-linking studies independently shows that Lp6.6 exists in multiple protein complexes in the outer membrane. We speculate that the function of Lp6.6 is connected to the physiological processes of these membrane complexes. Further characterization of differentially produced membrane antigens and associated protein complexes will likely aid in our understanding of the molecular details of B. burgdorferi persistence and transmission through a complex enzootic cycle.
Promnares
Kamoltip
K
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
Kumar
Manish
M
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
Shroder
Deborah Y
DY
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
Zhang
Xinyue
X
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
Anderson
John F
JF
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
Pal
Utpal
U
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D018884:Ixodes / Q000382:microbiology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008193:Lyme Disease / Q000635:transmission*; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; C103952:lipoprotein lp6.6, Borrelia burgdorferi
PLoS One. 2008 Aug 20;3(8):3010e
18714378
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15953-8
14671329
Mol Microbiol. 2007 Feb;63(3):694-710
17181780
Nature. 1997 Dec 11;390(6660):580-6
9403685
Mol Microbiol. 2000 Feb;35(3):490-516
10672174
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11405-10
12177443
Clin Microbiol Rev. 2005 Jul;18(3):484-509
16020686
PLoS Pathog. 2009 Feb;5(2):e1000293
19214205
PLoS Pathog. 2007 Mar;3(3):e33
17352535
Infect Immun. 2007 Jun;75(6):2786-94
17371860
J Clin Invest. 1995 Nov;96(5):2380-92
7593626
J Bacteriol. 2003 Nov;185(22):6723-7
14594849
Mol Microbiol. 2006 Mar;59(5):1473-84
16468989
Infect Immun. 2003 Jun;71(6):3371-83
12761121
Biochem Soc Trans. 2003 Feb;31(Pt 1):108-12
12546665
J Bacteriol. 2002 Aug;184(16):4536-43
12142424
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):670-5
11209063
Eur J Biochem. 2002 Jan;269(2):610-9
11856320
Anal Biochem. 1991 Dec;199(2):223-31
1812789
Mol Biotechnol. 1997 Oct;8(2):155-67
9406186
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3142-7
14970347
Mol Cell Proteomics. 2007 Feb;6(2):193-206
17092930
Infect Immun. 2002 Jul;70(7):3468-78
12065486
Mol Microbiol. 2006 Mar;59(5):1591-601
16468997
Appl Environ Microbiol. 2003 Jul;69(7):4116-22
12839789
Methods Enzymol. 2002;358:165-77
12474386
Annu Rev Entomol. 2008;53:323-43
17877457
PLoS Pathog. 2009 Mar;5(3):e1000326
19266024
Infect Immun. 2008 Aug;76(8):3374-89
18474646
Nature. 2005 Jul 28;436(7050):573-7
16049492
Appl Environ Microbiol. 1998 Apr;64(4):1313-8
9546166
Am J Trop Med Hyg. 1995 Oct;53(4):397-404
7485694
J Bacteriol. 2005 Nov;187(22):7845-52
16267308
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1562-7
11830671
J Infect Dis. 1993 May;167(5):1082-5
8486940
J Biol Chem. 2005 Oct 14;280(41):34409-19
16079137
Microbes Infect. 2006 Apr;8(5):1390-9
16698304
Mol Microbiol. 2007 Sep;65(5):1193-217
17645733
Infect Immun. 1997 Feb;65(2):412-21
9009290
Infect Immun. 2002 Apr;70(4):2139-50
11895980
Infect Immun. 2006 Jul;74(7):3864-73
16790758
J Clin Invest. 1998 May 15;101(10):2240-50
9593780
Infect Immun. 2004 Sep;72(9):5419-32
15322040
J Infect Dis. 2008 Jan 1;197(1):148-55
18171298
Infect Immun. 2003 Sep;71(9):5042-55
12933847
J Clin Invest. 2001 Mar;107(6):651-6
11254661
J Bacteriol. 2002 Jun;184(11):3122-5
12003955
J Biol Chem. 2008 Dec 12;283(50):34677-86
18801744
J Clin Microbiol. 1987 Mar;25(3):557-8
3571459
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5162-7
15743918
J Exp Med. 2008 Jan 21;205(1):133-41
18166585
Infect Immun. 2001 Jun;69(6):4159-63
11349092
J Clin Invest. 1997 Feb 1;99(3):377-9
9022068
J Exp Med. 2004 Mar 1;199(5):641-8
14981112
Microbiology (Reading). 2008 Nov;154(Pt 11):3420-3429
18957595
Infect Immun. 2006 Jun;74(6):3305-13
16714558
Infect Immun. 1992 Dec;60(12):4995-5003
1452330
Microb Pathog. 2000 Nov;29(5):279-87
11031122
Cell. 1998 Feb 6;92(3):291-4
9476889
J Clin Invest. 2004 Jan;113(2):220-30
14722614
Microbiology (Reading). 2008 Mar;154(Pt 3):979-988
18310044
Mol Microbiol. 2001 Jan;39(2):370-8
11136458
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6400-5
17404237