Citrobacter freundii fitness during bloodstream infection.

Citrobacter freundii fitness during bloodstream infection.
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DOI:
10.1038/s41598-018-30196-0
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发表时间:
2018-08-07
期刊:
影响因子:
4.6
通讯作者:
Mobley HLT
Mobley HLT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Anderson MT;Mitchell LA;Zhao L;Mobley HLT

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由血流中的微生物定植引起的败血症是与高死亡率相关的严重健康问题。本研究的目的是确定血流中弗氏柠檬酸杆菌的生理需求,作为由机会性革兰氏阴性病原体引起的菌血症的模型。对小鼠宿主进行的遗传筛选发现了177个对适应性有显着贡献的基因,其中大多数被广泛归类为具有代谢或细胞维持功能。在研究的途径中,达特蛋白分泌系统在竞争感染过程中赋予了最大的适应性贡献,并且推定的塔特分泌蛋白SufI也被确定为适应性因子。额外的工作集中在确定血流环境中细菌的相关代谢途径。在体外消除使用葡萄糖或甘露醇作为碳源的突变导致小鼠模型中的适应性丧失,并且在破坏半胱氨酸生物合成途径后获得了类似的结果。最后,在一组柠檬酸杆菌属血流分离株内以及柠檬酸杆菌属和粘质沙雷氏菌之间比较了已鉴定的适应因子的保守性,其结果表明存在血流环境中细菌存活和复制的保守策略。
Sepsis resulting from microbial colonization of the bloodstream is a serious health concern associated with high mortality rates. The objective of this study was to define the physiologic requirements of Citrobacter freundii in the bloodstream as a model for bacteremia caused by opportunistic Gram-negative pathogens. A genetic screen in a murine host identified 177 genes that contributed significantly to fitness, the majority of which were broadly classified as having metabolic or cellular maintenance functions. Among the pathways examined, the Tat protein secretion system conferred the single largest fitness contribution during competition infections and a putative Tat-secreted protein, SufI, was also identified as a fitness factor. Additional work was focused on identifying relevant metabolic pathways for bacteria in the bloodstream environment. Mutations that eliminated the use of glucose or mannitol as carbon sources in vitro resulted in loss of fitness in the murine model and similar results were obtained upon disruption of the cysteine biosynthetic pathway. Finally, the conservation of identified fitness factors was compared within a cohort of Citrobacter bloodstream isolates and between Citrobacter and Serratia marcescens, the results of which suggest the presence of conserved strategies for bacterial survival and replication in the bloodstream environment.
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