Fundamental differences in physiology of Bordetella pertussis dependent on the two-component system Bvg revealed by gene essentiality studies.

Fundamental differences in physiology of Bordetella pertussis dependent on the two-component system Bvg revealed by gene essentiality studies.
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DOI:
10.1099/mgen.0.000496
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发表时间:
2020-12
期刊:
影响因子:
3.9
通讯作者:
Preston A
Preston A
中科院分区:
生物学2区
文献类型:
--
作者:
Belcher T;MacArthur I;King JD;Langridge GC;Mayho M;Parkhill J;Preston A

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对细菌生长所必需的基因的鉴定揭示了许多关于细菌在不同条件下的基本生理学。 百日咳博德特氏菌是百日咳的病原体,通过双组分系统Bvg的活性,它可以处于强毒和无毒两种状态。B必需的基因使用转座子测序,对于不同的Bvg确定的生长状态,定义百日咳体外生长。此外,Bvg阶段之间的每个基因的插入指数的比较确定了那些基因的突变产生了显着不同的阶段之间的适应度成本。正如预期的那样,许多被鉴定为在其他细菌中生长所必需的基因也是B所必需的。百日咳。但是,某些基因的重要性依赖于Bvg。特别是,一些关键的细胞壁生物合成基因,包括整个mre/mrd基因座,是必不可少的生长的无毒(Bvg减)阶段,但不是有毒(Bvg加)阶段。此外,细胞壁的生物合成被确定为一个基本的过程,当中断产生更大的健身成本的Bvg负相相比,Bvg加阶段。Bvg负相生长比Bvg正相生长对细胞壁破坏抗生素氨苄青霉素更敏感,表明Bvg负相对细胞壁合成破坏的敏感性增加。这种Bvg依赖的条件必要性不是由于Bvg对细胞壁生物合成基因表达的调节;这表明这种基本过程在B中的Bvg阶段之间是不同的。百日咳,并且在Bvg减相更容易受到破坏。当考虑抗生素的作用时,细菌改变其细胞壁合成的能力是重要的,特别是如果开发靶向细胞壁合成的新药。
The identification of genes essential for a bacterium’s growth reveals much about its basic physiology under different conditions. Bordetella pertussis , the causative agent of whooping cough, adopts both virulent and avirulent states through the activity of the two-component system, Bvg. The genes essential for B. pertussis growth in vitro were defined using transposon sequencing, for different Bvg-determined growth states. In addition, comparison of the insertion indices of each gene between Bvg phases identified those genes whose mutation exerted a significantly different fitness cost between phases. As expected, many of the genes identified as essential for growth in other bacteria were also essential for B. pertussis . However, the essentiality of some genes was dependent on Bvg. In particular, a number of key cell wall biosynthesis genes, including the entire mre/mrd locus, were essential for growth of the avirulent (Bvg minus) phase but not the virulent (Bvg plus) phase. In addition, cell wall biosynthesis was identified as a fundamental process that when disrupted produced greater fitness costs for the Bvg minus phase compared to the Bvg plus phase. Bvg minus phase growth was more susceptible than Bvg plus phase growth to the cell wall-disrupting antibiotic ampicillin, demonstrating the increased susceptibility of the Bvg minus phase to disruption of cell wall synthesis. This Bvg-dependent conditional essentiality was not due to Bvg-regulation of expression of cell wall biosynthesis genes; suggesting that this fundamental process differs between the Bvg phases in B. pertussis and is more susceptible to disruption in the Bvg minus phase. The ability of a bacterium to modify its cell wall synthesis is important when considering the action of antibiotics, particularly if developing novel drugs targeting cell wall synthesis.
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