Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.
Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.
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DOI：
10.1371/journal.pgen.1002377
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发表时间：
2011-11
期刊：
影响因子：
4.5
通讯作者：
Emili A
中科院分区：
文献类型：
--
作者：
Babu M;Díaz-Mejía JJ;Vlasblom J;Gagarinova A;Phanse S;Graham C;Yousif F;Ding H;Xiong X;Nazarians-Armavil A;Alamgir M;Ali M;Pogoutse O;Pe'er A;Arnold R;Michaut M;Parkinson J;Golshani A;Whitfield C;Wodak SJ;Moreno-Hagelsieb G;Greenblatt JF;Emili A
细菌细胞膜作为微生物与环境之间的界面，具有广泛的生物学意义和临床意义。虽然许多生物合成基因和途径已经被孤立地识别和研究，但这些基因和途径如何在功能上相交，以确保在适应环境挑战的反应中包膜的完整性仍不清楚。为此，我们进行了高密度合成遗传筛选，以生成定量的功能关联图，几乎涵盖了营养缺陷型(富营养型)和原养型(最低营养型)培养条件下大肠杆菌的整个细胞膜生物合成机制。在测试的235,000个双基因突变组合中检测到的遗传相互作用的不同模式揭示了意外的特定条件的功能串扰和确保抗压包膜组装和维护的遗传备份机制。这些网络还提供了对全球系统连通性和普遍细菌结构的动态功能重组的见解，这种结构在真细菌(包括病原体)中广泛保守，也是一个重要的靶标。细胞膜的正确组装对细菌的生长、环境适应和耐药性是至关重要的。然而，尽管参与细胞被膜生物合成的许多基因和途径的生物学作用已经被广泛地孤立地研究，但在不同的生长条件下，无数的成分如何在功能上相交以保持被膜的完整性还没有被系统地探索。基因组规模的遗传相互作用筛选越来越多地在酵母中产生重大影响；尽管细菌在人类健康和疾病中的重要性，但尚未有关于细菌的类似全面研究的报道。我们通过使用合成基因阵列技术来生成遗传相互作用的定量图谱，该图谱几乎涵盖了经典模式大肠杆菌在两种常见的实验室生长条件(丰富和最低培养条件)下细胞膜生物合成机制的所有组件。从得到的高置信度遗传相互作用网络中，我们确定了包膜组装和确保包膜在环境挑战下完整性的遗传备份机制的全球重塑基础上的特定条件的功能依赖。
As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. Proper assembly of the cell envelope is essential for bacterial growth, environmental adaptation, and drug resistance. Yet, while the biological roles of the many genes and pathways involved in biosynthesis of the cell envelope have been studied extensively in isolation, how the myriad components intersect functionally to maintain envelope integrity under different growth conditions has not been explored systematically. Genome-scale genetic interaction screens have increasingly been performed to great impact in yeast; no analogous comprehensive studies have yet been reported for bacteria despite their prominence in human health and disease. We addressed this by using a synthetic genetic array technology to generate quantitative maps of genetic interactions encompassing virtually all the components of the cell envelope biosynthetic machinery of the classic model bacterium E. coli in two common laboratory growth conditions (rich and minimal medium). From the resulting networks of high-confidence genetic interactions, we identify condition-specific functional dependencies underlying envelope assembly and global remodeling of genetic backup mechanisms that ensure envelope integrity under environmental challenge.
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影响因子：
14.9
作者：
Geissmann T;Chevalier C;Cros MJ;Boisset S;Fechter P;Noirot C;Schrenzel J;François P;Vandenesch F;Gaspin C;Romby P
通讯作者：
Romby P
影响因子：
48
作者：
Butland, Gareth;Babu, Mohan;Emili, Andrew
通讯作者：
Emili, Andrew
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：
--
影响因子：
12.3
作者：
Collins SR;Schuldiner M;Krogan NJ;Weissman JS
通讯作者：
Weissman JS
影响因子：
11.3
作者：
Díaz-Mejía JJ;Babu M;Emili A
通讯作者：
Emili A