Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.
Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.
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DOI：
10.1371/journal.pgen.1009586
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发表时间：
2021-12
期刊：
影响因子：
4.5
通讯作者：
Henderson IR
中科院分区：
文献类型：
--
作者：
Goodall ECA;Isom GL;Rooke JL;Pullela K;Icke C;Yang Z;Boelter G;Jones A;Warner I;Da Costa R;Zhang B;Rae J;Tan WB;Winkle M;Delhaye A;Heinz E;Collet JF;Cunningham AF;Blaskovich MA;Parton RG;Cole JA;Banzhaf M;Chng SS;Vollmer W;Bryant JA;Henderson IR
细胞被膜对于生命的所有领域的生存能力都是必不可少的。它将酶和底物保留在有限的空间内，同时为外部环境提供保护屏障。破坏细菌病原体包膜的稳定性是抗微生物治疗所采用的常见策略。然而，即使在研究得最好的生物之一大肠杆菌中，我们对细胞包膜连续层的合成在生长和细胞分裂过程中如何协调的理解仍然存在差距。在这里，我们使用全基因组表型筛选来鉴定具有缺陷细胞包膜的突变体。我们报告说，损失yhcB，一个保守的基因的未知功能，结果在损失的信封稳定性，增加细胞通透性和失调的控制细胞大小。使用全基因组转座子诱变策略，我们报告了yhcB的综合遗传相互作用网络，揭示了所有基因的合成负和合成正关系。这些基因包括先前报道的在细胞被膜生物发生中起作用的基因。令人惊讶的是，我们鉴定出了先前注释为必需的基因，这些基因在ΔyhcB背景下变得非必需。随后的分析表明，YhcB的功能在几个信封生物合成途径的交界处协调时空的细胞生长，突出YhcB作为一个尚未开发的抗菌靶标。所有的生命都依赖于细胞膜来包裹使生命成为可能的化学反应。但是细胞膜是如何生长的呢？细胞被膜的每种成分如何在正确的时间、正确的位置以正确的量被整合到被膜中，以防止细胞死亡，这是细菌学中一个长期存在的问题。使用高通量化学遗传筛选的独特组合，我们确定了yhcB，一个保守的基因，未知的功能，需要在大肠杆菌细胞包膜的完整性的维护。YhcB的缺失导致由过量膜磷脂的产生驱动的异常细胞大小。随后的分子和生物化学分析表明，YhcB影响LPS，肽聚糖和膜磷脂的时空生物合成。我们的数据表明，YhcB是革兰氏阴性细菌中细胞包膜生长的关键调节因子，在协调细胞宽度、伸长和分裂以维持细胞包膜完整性方面起着至关重要的作用。
The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment. However, even in one of the best studied organisms, Escherichia coli, there remain gaps in our understanding of how the synthesis of the successive layers of the cell envelope are coordinated during growth and cell division. Here, we used a whole-genome phenotypic screen to identify mutants with a defective cell envelope. We report that loss of yhcB, a conserved gene of unknown function, results in loss of envelope stability, increased cell permeability and dysregulated control of cell size. Using whole genome transposon mutagenesis strategies, we report the comprehensive genetic interaction network of yhcB, revealing all genes with a synthetic negative and a synthetic positive relationship. These genes include those previously reported to have a role in cell envelope biogenesis. Surprisingly, we identified genes previously annotated as essential that became non-essential in a ΔyhcB background. Subsequent analyses suggest that YhcB functions at the junction of several envelope biosynthetic pathways coordinating the spatiotemporal growth of the cell, highlighting YhcB as an as yet unexplored antimicrobial target. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the correct amount, in the correct place, and at the correct time, to prevent cell death, has been a long-standing question in bacteriology. Using a unique combination of high throughput chemical genetic screens we identified yhcB, a conserved gene of unknown function, required for the maintenance of cell envelope integrity in Escherichia coli. Loss of YhcB results in aberrant cell size driven by the production of excess membrane phospholipids. Subsequent molecular and biochemical analyses suggest YhcB influences the spatiotemporal biogenesis of LPS, peptidoglycan and membrane phospholipids. Our data indicate YhcB is a key regulator of cell envelope growth in Gram-negative bacteria playing a crucial role in coordinating cell width, elongation, and division to maintain cell envelope integrity.
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影响因子：
14.9
作者：
Buchan, Daniel W. A.;Jones, David T.
通讯作者：
Jones, David T.
影响因子：
4.9
作者：
DIXON, RA;CHOPRA, I
通讯作者：
CHOPRA, I
影响因子：
44.1
作者：
Chi X;Fan Q;Zhang Y;Liang K;Wan L;Zhou Q;Li Y
通讯作者：
Li Y
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL