Campylobacter jejuni pdxA affects flagellum-mediated motility to alter host colonization.

Campylobacter jejuni pdxA affects flagellum-mediated motility to alter host colonization.
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DOI:
10.1371/journal.pone.0070418
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yamamoto S
Yamamoto S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Asakura H;Hashii N;Uema M;Kawasaki N;Sugita-Konishi Y;Igimi S;Yamamoto S

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维生素B6(吡哆醛-5'-磷酸,PLP)与原核生物的多种生物功能有关。在这里,我们报道了pdxA(假定的4-羟基- l -苏氨酸磷酸脱氢酶)基因在鞭毛运动的plp依赖性调节中起关键作用,从而改变了主要食源性病原体空肠弯曲杆菌的宿主定植。空肠C. pdxA突变体不能产生PLP,同时也表现出鞭毛运动的丧失。质谱分析显示,主要鞭毛聚糖假氨基酸(Pse)的3倍减少与pdxA的破坏有关。与WT菌株相比,pdxA突变体的生长速度也有所降低。比较代谢组学分析揭示了WT C. jejuni和pdxA突变体在呼吸/能量代谢方面的差异,为两株菌株之间的生长适应性差异提供了可能的解释。与缺乏鞭毛运动性一致,pdxA突变体在INT407细胞中表现出运动性介导的反应(细菌粘附、ERK1/2激活和IL-8产生)受损,与WT菌株相比,鸡的定植减少。总体而言,本研究表明pdxA基因影响plp介导的鞭毛运动功能,主要是通过Pse修饰的改变,而该基因的破坏也会改变呼吸/能量代谢,从而潜在地影响宿主定植。因此,我们的数据提出了关于PLP及其依赖酶作为控制家禽宿主中这种病原体的有效靶点的新含义。
Vitamin B6 (pyridoxal-5'-phosphate, PLP) is linked to a variety of biological functions in prokaryotes. Here, we report that the pdxA (putative 4-hydroxy-L-threonine phosphate dehydrogenase) gene plays a pivotal role in the PLP-dependent regulation of flagellar motility, thereby altering host colonization in a leading foodborne pathogen, Campylobacter jejuni. A C. jejuni pdxA mutant failed to produce PLP and exhibited a coincident loss of flagellar motility. Mass spectrometric analyses showed a 3-fold reduction in the main flagellar glycan pseudaminic acid (Pse) associated with the disruption of pdxA. The pdxA mutant also exhibited reduced growth rates compared with the WT strain. Comparative metabolomic analyses revealed differences in respiratory/energy metabolism between WT C. jejuni and the pdxA mutant, providing a possible explanation for the differential growth fitness between the two strains. Consistent with the lack of flagellar motility, the pdxA mutant showed impaired motility-mediated responses (bacterial adhesion, ERK1/2 activation, and IL-8 production) in INT407 cells and reduced colonization of chickens compared with the WT strain. Overall, this study demonstrated that the pdxA gene affects the PLP-mediated flagellar motility function, mainly through alteration of Pse modification, and the disruption of this gene also alters the respiratory/energy metabolisms to potentially affect host colonization. Our data therefore present novel implications regarding the utility of PLP and its dependent enzymes as potent target(s) for the control of this pathogen in the poultry host.
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