Role of the wbt locus of Francisella tularensis in lipopolysaccharide O-antigen biogenesis and pathogenicity

被引:81
作者
Raynaud, Catherine
Meibom, Karin L.
Lety, Marie-Annick
Dubail, Iharilalao
Candela, Thomas
Frapy, Eric
Charbit, Alain
机构
[1] Univ Paris Descartes, Fac Med Rene Descartes, F-75015 Paris, France
[2] INSERM, U570, Unite Pathogenie Infect Syst, F-75015 Paris, France
[3] CNRS, URA2172, Unite Toxines & Pathogenie Bacterienne, F-75724 Paris, France
关键词
D O I
10.1128/IAI.01429-06
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Francisella tularensis is a highly infectious bacterial pathogen, responsible for the zoonotic disease tularemia. We screened a bank of transposon insertion mutants of F. tularensis subsp. holarctica LVS for colony morphology alterations and selected a mutant with a transposon insertion in wbtA, the first gene of the predicted lipopolysaccharide O-antigen gene cluster. Inactivation of wbtA led to the complete loss of O antigen, conferred serum sensitivity, impaired intracellular replication, and severely attenuated virulence in the mouse model. Notably, this mutant afforded protection against a challenge against virulent LVS.
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收藏
页码:536 / 541
页数:6
相关论文
共 23 条
[1]   Functional analysis of genes responsible for the synthesis of the B-band O antigen of Pseudomonas aeruginosa serotype O6 lipopolysaccharide [J].
Bélanger, M ;
Burrows, LL ;
Lam, JS .
MICROBIOLOGY-UK, 1999, 145 :3505-3521
[2]   EVALUATION OF LIVE TULAREMIA VACCINE PREPARED IN A CHEMICALLY DEFINED MEDIUM [J].
CHAMBERL.RE .
APPLIED MICROBIOLOGY, 1965, 13 (02) :232-&
[3]   INCREASED ENCAPSULATION AND VIRULENCE OF FRANCISELLA-TULARENSIS LIVE VACCINE STRAIN (LVS) BY SUBCULTURING ON SYNTHETIC MEDIUM [J].
CHERWONOGRODZKY, JW ;
KNODEL, MH ;
SPENCE, MR .
VACCINE, 1994, 12 (09) :773-775
[4]   Mice intradermally-inoculated with the intact lipopolysaccharide, but not the lipid A or O-chain, from Francisella tularensis LVS rapidly acquire varying degrees of enhanced resistance against systemic or aerogenic challenge with virulent strains of the pathogen [J].
Conlan, JW ;
Vinogradov, E ;
Monteiro, MA ;
Perry, MB .
MICROBIAL PATHOGENESIS, 2003, 34 (01) :39-45
[5]   Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen [J].
Conlan, JW ;
Shen, H ;
Webb, A ;
Perry, MB .
VACCINE, 2002, 20 (29-30) :3465-3471
[6]   Isolation and characterization of Francisella novicida mutants defective in lipopolysaccharide biosynthesis [J].
Cowley, SC ;
Gray, CJ ;
Nano, FE .
FEMS MICROBIOLOGY LETTERS, 2000, 182 (01) :63-67
[7]   Phase variation in Francisella tularensis affecting intracellular growth, lipopolysaccharide antigenicity and nitric oxide production [J].
Cowley, SC ;
Myltseva, SV ;
Nano, FE .
MOLECULAR MICROBIOLOGY, 1996, 20 (04) :867-874
[8]   USE OF IMMUNOELECTRON MICROSCOPY TO DEMONSTRATE FRANCISELLA-TULARENSIS [J].
GEISBERT, TW ;
JAHRLING, PB ;
EZZELL, JW .
JOURNAL OF CLINICAL MICROBIOLOGY, 1993, 31 (07) :1936-1939
[9]   Grey variants of the live vaccine strain of Francisella tularensis lack lipopolysaccharide O-antigen, show reduced ability to survive in macrophages and do not induce protective immunity in mice [J].
Hartley, G ;
Taylor, R ;
Prior, J ;
Newstead, S ;
Hitchen, PG ;
Morris, HR ;
Dell, A ;
Titball, RW .
VACCINE, 2006, 24 (07) :989-996
[10]   Use of transposon-transposase complexes to create stable insertion mutant strains of Francisella tularensis LVS [J].
Kawula, TH ;
Hall, JD ;
Fuller, JR ;
Craven, RR .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2004, 70 (11) :6901-6904