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.

中文翻译：

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基因必要性研究揭示了百日咳博德特氏菌生理学的根本差异依赖于双组分系统 Bvg


细菌生长必需基因的鉴定揭示了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，呈现有毒力和无毒力状态。对于不同的 Bvg 确定的生长状态，使用转座子测序定义了百日咳博德特氏菌体外生长所必需的基因。此外，比较 Bvg 阶段之间每个基因的插入指数，识别出其突变在阶段之间产生显着不同的适应度成本的基因。正如预期的那样，许多被确定为其他细菌生长所必需的基因对于百日咳博德特氏菌也是必需的。然而，某些基因的重要性取决于 Bvg。特别是，许多关键的细胞壁生物合成基因，包括整个mre / mrd基因座，对于无毒（Bvg 负）阶段的生长至关重要，但对于有毒（Bvg 正）阶段的生长则不然。此外，细胞壁生物合成被认为是一个基本过程，与 Bvg 正相相比，当 Bvg 负相被破坏时，会产生更大的适应成本。 Bvg负相生长比Bvg正相生长对破坏细胞壁的抗生素氨苄西林更敏感，这表明Bvg负相对破坏细胞壁合成的敏感性增加。 这种 Bvg 依赖性条件必要性并不是由于 Bvg 对细胞壁生物合成基因表达的调节；表明百日咳博德特氏菌的 Bvg 阶段之间的这一基本过程有所不同，并且更容易受到 Bvg 负阶段的破坏。在考虑抗生素的作用时，细菌改变其细胞壁合成的能力非常重要，特别是在开发针对细胞壁合成的新药物时。