title: Borrelia burgdorferi bba66 gene inactivation results in attenuated mouse infection by tick transmission.
abstract: The impact of the Borrelia burgdorferi surface-localized immunogenic lipoprotein BBA66 on vector and host infection was evaluated by inactivating the encoding gene, bba66, and characterizing the mutant phenotype throughout the natural mouse-tick-mouse cycle. The BBA66-deficient mutant isolate, Bb(ΔA66), remained infectious in mice by needle inoculation of cultured organisms, but differences in spirochete burden and pathology in the tibiotarsal joint were observed relative to the parental wild-type (WT) strain. Ixodes scapularis larvae successfully acquired Bb(ΔA66) following feeding on infected mice, and the organisms persisted in these ticks through the molt to nymphs. A series of tick transmission experiments (n = 7) demonstrated that the ability of Bb(ΔA66)-infected nymphs to infect laboratory mice was significantly impaired compared to that of mice fed upon by WT-infected ticks. trans-complementation of Bb(ΔA66) with an intact copy of bba66 restored the WT infectious phenotype in mice via tick transmission. These results suggest a role for BBA66 in facilitating B. burgdorferi dissemination and transmission from the tick vector to the mammalian host as part of the disease process for Lyme borreliosis.
authors: National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Bacterial Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
authors: Toni G
authors: TG
authors: Patton
authors: Kevin S
authors: KS
authors: Brandt
authors: Christi
authors: C
authors: Nolder
authors: Dawn R
authors: DR
authors: Clifton
authors: James A
authors: JA
authors: Carroll
authors: Robert D
authors: RD
authors: Gilmore
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001096:Arachnid Vectors / Q000382:microbiology / Q000502:physiology; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D018884:Ixodes / Q000382:microbiology* / Q000502:physiology; D007814:Larva / Q000382:microbiology / Q000502:physiology; D008193:Lyme Disease / Q000382:microbiology / Q000635:transmission*; D051379:Mice; D008809:Mice, Inbred C3H; D016254:Mutagenesis, Insertional; D014158:Transcription, Genetic
chemical_list: D000942:Antigens, Bacterial; C513741:BBA66 protein, Borrelia burgdorferi
references: Infect Immun. 2012 Oct;80(10):3501-11
references: 22851744
references: Microb Pathog. 2008 Nov-Dec;45(5-6):355-60
references: 18848981
references: Infect Immun. 2003 Jun;71(6):3371-83
references: 12761121
references: J Infect Dis. 2010 Apr 1;201(7):1084-95
references: 20170377
references: Mol Microbiol. 2011 Jul;81(1):219-31
references: 21542866
references: Infect Immun. 2008 Sep;76(9):3844-53
references: 18573895
references: PLoS Pathog. 2011 Jun;7(6):e1002079
references: 21695244
references: Mol Microbiol. 2012 Sep;85(6):1105-18
references: 22758390
references: PLoS Pathog. 2007 Mar;3(3):e33
references: 17352535
references: Infect Immun. 2006 Jun;74(6):3554-64
references: 16714588
references: Infect Immun. 2008 Jun;76(6):2498-511
references: 18390998
references: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1562-7
references: 11830671
references: J Exp Med. 2004 Mar 1;199(5):641-8
references: 14981112
references: Mol Microbiol. 2006 Jul;61(1):243-58
references: 16824109
references: Infect Immun. 2010 Jul;78(7):2910-8
references: 20421380
references: Mol Microbiol. 2007 Feb;63(3):694-710
references: 17181780
references: Infect Immun. 2011 Mar;79(3):1208-17
references: 21173312
references: J Bacteriol. 1996 Oct;178(20):5946-53
references: 8830691
references: Infect Immun. 2004 Aug;72(8):4864-7
references: 15271949
references: Infect Immun. 2003 Apr;71(4):1689-705
references: 12654782
references: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6972-7
references: 15860579
references: PLoS Pathog. 2011 Jul;7(7):e1002102
references: 21750672
references: PLoS One. 2011 May 03;6(5):e19536
references: 21559293
references: Microbiology (Reading). 2008 Sep;154(Pt 9):2641-2658
references: 18757798
references: Infect Immun. 2006 Jan;74(1):296-304
references: 16368984
references: Infect Immun. 2005 Nov;73(11):7398-405
references: 16239539
references: Infect Immun. 2000 Dec;68(12):6677-84
references: 11083781
references: Infect Immun. 2008 Nov;76(11):5274-84
references: 18765733
references: Microbiology (Reading). 2003 Jul;149(Pt 7):1819-1828
references: 12855733
references: J Microbiol Methods. 2011 Aug;86(2):243-7
references: 21605603
references: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7515-20
references: 20368453
references: J Mol Microbiol Biotechnol. 2003;6(1):29-40
references: 14593251
references: Mol Microbiol. 2007 Sep;65(5):1193-217
references: 17645733
references: Infect Immun. 2002 Apr;70(4):2139-50
references: 11895980
references: Infect Immun. 2006 Jul;74(7):3864-73
references: 16790758
references: Infect Immun. 2008 Dec;76(12):5694-705
references: 18809667
references: Infect Immun. 2004 Sep;72(9):5419-32
references: 15322040
references: J Infect Dis. 2008 Jan 1;197(1):148-55
references: 18171298
references: Infect Immun. 2010 Jan;78(1):100-7
references: 19822648
references: PLoS Pathog. 2012 Feb;8(2):e1002532
references: 22359504
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5162-7
references: 15743918
references: Infect Immun. 2010 Jun;78(6):2397-407
references: 20231410
references: J Clin Microbiol. 1989 Aug;27(8):1723-7
references: 2768461
references: Infect Immun. 2011 Aug;79(8):3117-30
references: 21606185
references: J Bacteriol. 2000 May;182(9):2445-52
references: 10762244
references: Infect Immun. 2007 Jun;75(6):2753-64
references: 17371862
references: J Bacteriol. 2009 Oct;191(20):6231-41
references: 19666713
references: Infect Immun. 1994 Feb;62(2):492-500
references: 8300208
references: Infect Immun. 2008 Mar;76(3):1239-46
references: 18195034
references: PLoS Pathog. 2011 Jun;7(6):e1002133
references: 21738477
references: Mol Microbiol. 2009 Oct;74(1):112-125
references: 19703109
references: Mol Microbiol. 2007 Oct;66(1):262-76
references: 17784908
references: Infect Immun. 2000 Mar;68(3):1222-30
references: 10678930
references: Infect Immun. 2012 Jul;80(7):2485-92
references: 22508862