Genomics and Experimental Analysis Reveal a Novel Factor Contributing to the Virulence of Cronobacter sakazakii Strains Associated With Neonate Infection.
Genomics and Experimental Analysis Reveal a Novel Factor Contributing to the Virulence of Cronobacter sakazakii Strains Associated With Neonate Infection.
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DOI：
10.1093/infdis/jiz098
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发表时间：
2019-06
期刊：
影响因子：
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通讯作者：
Min Wang;Lu Wang;Pan Wu;Tingting Chen;Yiming Zhu;Yang Zhang;Yi Wei;Chengqian Qian;Yuhui W
中科院分区：
文献类型：
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作者：
Min Wang;Lu Wang;Pan Wu;Tingting Chen;Yiming Zhu;Yang Zhang;Yi Wei;Chengqian Qian;Yuhui W
坂崎克罗伊氏菌引起早产儿脑膜炎和坏死性小肠结肠炎。然而，它的毒力决定因素，特别是那些特定的新生儿感染相关的菌株，仍然在很大程度上是未知的。方法对209株C.结果表明，坂崎木的基因组中有8个克隆群（CG）。结果发现CG 1和CG 2与新生儿感染显著相关，并确定了这两个CGs的显著流行基因。其中，编码LysR型调节因子CklR的基因在动物实验中被证明有助于细菌的致病性。我们发现CklR直接结合并激活suf Fe-S簇生物合成操纵子，并且suf操纵子的高表达增加细菌对氧化应激的抗性，这增加了宿主内的存活。这会导致高度的菌血症，这有助于脑膜炎的发展。结论我们的工作揭示了一种新的特异于主要致病性C.坂崎菌株
BACKGROUND Cronobacter sakazakii causes meningitis and necrotizing enterocolitis in premature infants. However, its virulence determinants, especially those specific for strains associated with neonate infections, remain largely unknown. METHODS In this study, we performed a comparative genomic analysis of 209 C. sakazakii genomes, and 8 clonal groups (CGs) were revealed. RESULTS CG1 and CG2 were found to be significantly associated with neonate infections, and significantly prevalent genes in these 2 CGs were identified. Of these, a gene encoding the LysR-type regulator, CklR, was shown to contribute to bacterial pathogenicity based on animal experiments. We found that CklR directly binds and activates the suf Fe-S cluster biosynthesis operon, and high expression of the suf operon increases bacterial resistance to oxidative stress, which increases survival within the host. This leads to a high degree of bacteremia, which contributes to the development of meningitis. CONCLUSIONS Our work revealed a novel virulence factor specific to predominant pathogenic C. sakazakii strains.