Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice

被引:45
作者
Santos Lacerda, Thais Lourdes [1 ]
Cardoso, Patricia Gomes [2 ]
de Almeida, Leonardo Augusto [1 ]
Baratella da Cunha Camargo, Ilana Lopes [3 ]
Freitas Afonso, Daniela Almeida [1 ]
Trant, Cyntia Cardoso [1 ]
Macedo, Gilson Costa [1 ]
Campos, Eleonora [4 ]
Cravero, Silvio L. [4 ]
Salcedo, Suzana P. [5 ,6 ,7 ]
Gorvel, Jean-Pierre [5 ,6 ,7 ]
Oliveira, Sergio Costa [1 ]
机构
[1] Univ Fed Minas Gerais, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Lavras, Dept Biol, Lavras, Brazil
[3] Univ Sao Paulo, Phys Inst Sao Carlos, Dept Phys & Informat, Sao Carlos, SP, Brazil
[4] INTA Castelar, Inst Biotecnol, Buenos Aires, DF, Argentina
[5] Aix Marseille Univ, Fac Sci Luminy, Ctr Immunol Marseille Luminy, Marseille, France
[6] INSERM, U631, F-13258 Marseille, France
[7] CNRS, UMR6102, Marseille, France
关键词
Brucella abortus; Rough strain; Live vaccine; LIPOPOLYSACCHARIDE O-ANTIGEN; ENDOPLASMIC-RETICULUM; MURINE MACROPHAGES; MELITENSIS; 16M; VACCINES; MUTANTS; RB51; POLYSACCHARIDE; PATHOGENESIS; PHENOTYPE;
D O I
10.1016/j.vaccine.2010.06.023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rough mutants of Brucella abortus were generated by disruption of wbkC gene which encodes the formyltransferase enzyme involved in LPS biosynthesis. In bone marrow-derived macrophages the B. abortus Delta wbkC mutants were attenuated, could not reach a replicative niche and induced higher levels of IL-12 and TNF-alpha when compared to parental smooth strains. Additionally, mutants exhibited attenuation in vivo in C57BL/6 and interferon regulatory factor-1 knockout mice. Delta wbkC mutant strains induced lower protective immunity in C56BL/6 than smooth vaccine S19 but similar to rough vaccine RB51. Finally, we demonstrated that Brucella wbkC is critical for LPS biosynthesis and full bacterial virulence. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5627 / 5634
页数:8
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