Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response

被引:124
作者
Centurion-Lara, A [1 ]
Castro, C [1 ]
Barrett, L [1 ]
Cameron, C [1 ]
Mostowfi, M [1 ]
Van Voorhis, WC [1 ]
Lukehart, SA [1 ]
机构
[1] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA
关键词
syphilis; vaccine; subpopulation; surface antigens; antigenic variation;
D O I
10.1084/jem.189.4.647
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity;during syphilis infection.
引用
收藏
页码:647 / 656
页数:10
相关论文
共 45 条
[1]   Tromp1, a putative rare outer membrane protein, is anchored by an uncleaved signal sequence to the Treponema pallidum cytoplasmic membrane [J].
Akins, DR ;
Robinson, E ;
Shevchenko, D ;
Elkins, C ;
Cox, DL ;
Radolf, JD .
JOURNAL OF BACTERIOLOGY, 1997, 179 (16) :5076-5086
[2]   MACROPHAGE-MEDIATED KILLING OF OPSONIZED TREPONEMA-PALLIDUM [J].
BAKERZANDER, SA ;
LUKEHART, SA .
JOURNAL OF INFECTIOUS DISEASES, 1992, 165 (01) :69-74
[3]   VDRL ANTIBODIES ENHANCE PHAGOCYTOSIS OF TREPONEMA-PALLIDUM BY MACROPHAGES [J].
BAKERZANDER, SA ;
SHAFFER, JM ;
LUKEHART, SA .
JOURNAL OF INFECTIOUS DISEASES, 1993, 167 (05) :1100-1105
[4]   VARIABLE ANTIGEN GENES OF THE RELAPSING FEVER AGENT BORRELIA-HERMSII ARE ACTIVATED BY PROMOTER ADDITION [J].
BARBOUR, AG ;
BURMAN, N ;
CARTER, CJ ;
KITTEN, T ;
BERGSTROM, S .
MOLECULAR MICROBIOLOGY, 1991, 5 (02) :489-493
[5]   Monitoring urinary excretion of 5-hydroxymethyluracil for assessment of oxidative DNA damage and repair [J].
Bianchini, F ;
Hall, H ;
Donato, F ;
Cadet, J .
BIOMARKERS, 1996, 1 (03) :178-184
[6]  
BISHOP NH, 1976, J IMMUNOL, V117, P197
[7]   ISOLATION OF THE OUTER MEMBRANES FROM TREPONEMA-PALLIDUM AND TREPONEMA-VINCENTII [J].
BLANCO, DR ;
REIMANN, K ;
SKARE, J ;
CHAMPION, CI ;
FOLEY, D ;
EXNER, MM ;
HANCOCK, REW ;
MILLER, JN ;
LOVETT, MA .
JOURNAL OF BACTERIOLOGY, 1994, 176 (19) :6088-6099
[8]  
BLANCO DR, 1990, J IMMUNOL, V144, P1914
[9]   IDENTIFICATION OF TREPONEMA-PALLIDUM SUBSPECIES PALLIDUM GENES ENCODING SIGNAL PEPTIDES AND MEMBRANE-SPANNING SEQUENCES USING A NOVEL ALKALINE-PHOSPHATASE EXPRESSION VECTOR [J].
BLANCO, DR ;
GILADI, M ;
CHAMPION, CI ;
HAAKE, DA ;
CHIKAMI, GK ;
MILLER, JN ;
LOVETT, MA .
MOLECULAR MICROBIOLOGY, 1991, 5 (10) :2405-2415
[10]  
BLANCO DR, 1984, J IMMUNOL, V133, P2693