Identification of Burkholderia cenocepacia Strain H111 Virulence Factors Using Nonmammalian Infection Hosts

Identification of Burkholderia cenocepacia Strain H111 Virulence Factors Using Nonmammalian Infection Hosts
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DOI:
10.1128/iai.00768-12
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发表时间:
2013-01-01
影响因子:
3.1
通讯作者:
Eberl, Leo
Eberl, Leo
中科院分区:
医学2区
文献类型:
--
作者:
Schwager, Stephan;Agnoli, Kirsty;Eberl, Leo

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新洋葱伯克霍尔德氏菌H111,一种从囊性纤维化患者中分离的菌株,已被证明能有效杀死线虫秀丽隐杆线虫。我们用了C。elegans感染模型筛选B. cenocepacia H111的毒力减弱。在大约5,500个B。新洋葱H111随机mini-Tn 5插入突变体中,有22株在新洋葱中表现出弱毒。优美的除了群体感应调节cepR,没有突变的基因编码的生物合成的经典毒力因子,如胞外蛋白酶或铁载体。相反,突变体包含代谢和调节基因的插入。突变体在C. elegans感染模型中的那些也在果蝇针刺模型中进行了测试,并且在该模型中也减毒的那些在大蜡螟中进一步进行了测试。22个突变株中有6个在D.其中5株在G. Mellonella模型。我们表明,基因编码的嘌呤,嘧啶和莽草酸生物合成途径的酶是至关重要的多宿主感染模型的毒力。
Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence. Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases or siderophores. Instead, the mutants contained insertions in metabolic and regulatory genes. Mutants attenuated in virulence in the C. elegans infection model were also tested in the Drosophila melanogaster pricking model, and those also attenuated in this model were further tested in Galleria mellonella. Six of the 22 mutants were attenuated in D. melanogaster, and five of these were less pathogenic in the G. mellonella model. We show that genes encoding enzymes of the purine, pyrimidine, and shikimate biosynthesis pathways are critical for virulence in multiple host models of infection.