Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

被引:84
作者
Babu, Mohan [1 ]
Diaz-Mejia, J. Javier [1 ,2 ]
Vlasblom, James [3 ,4 ]
Gagarinova, Alla [1 ,5 ]
Phanse, Sadhna [1 ]
Graham, Chris [1 ]
Yousif, Fouad [1 ]
Ding, Huiming [1 ]
Xiong, Xuejian [3 ]
Nazarians-Armavil, Anaies [1 ]
Alamgir, Md [6 ,7 ]
Ali, Mehrab [1 ]
Pogoutse, Oxana [1 ]
Pe'er, Asaf [8 ]
Arnold, Roland [1 ]
Michaut, Magali [1 ]
Parkinson, John [3 ,4 ,5 ]
Golshani, Ashkan [6 ,7 ]
Whitfield, Chris [9 ]
Wodak, Shoshana J. [3 ,4 ,5 ]
Moreno-Hagelsieb, Gabriel [2 ]
Greenblatt, Jack F. [1 ,5 ]
Emili, Andrew [1 ,5 ]
机构
[1] Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr, Toronto, ON, Canada
[2] Wilfrid Laurier Univ, Dept Biol, Waterloo, ON N2L 3C5, Canada
[3] Hosp Sick Children, Toronto, ON M5G 1X8, Canada
[4] Univ Toronto, Dept Biochem, Toronto, ON, Canada
[5] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
[6] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada
[7] Carleton Univ, Ottawa Inst Syst Biol, Ottawa, ON K1S 5B6, Canada
[8] Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Microbiol & Mol Genet, Jerusalem, Israel
[9] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada
来源
PLOS GENETICS | 2011年 / 7卷 / 11期
基金
加拿大健康研究院;
关键词
OUTER-MEMBRANE BIOGENESIS; SMALL NONCODING RNAS; INDUCED LYSIS; PROTEIN; COMPLEX; LIPOPOLYSACCHARIDE; IDENTIFICATION; TRANSPORT; DIVISION; ORGANIZATION;
D O I
10.1371/journal.pgen.1002377
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:15
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