title: Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.
abstract: 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.
authors: Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Canada. mohan.babu@utoronto.ca
authors: Mohan
authors: M
authors: Babu
authors: J Javier
authors: JJ
authors: Díaz-Mejía
authors: James
authors: J
authors: Vlasblom
authors: Alla
authors: A
authors: Gagarinova
authors: Sadhna
authors: S
authors: Phanse
authors: Chris
authors: C
authors: Graham
authors: Fouad
authors: F
authors: Yousif
authors: Huiming
authors: H
authors: Ding
authors: Xuejian
authors: X
authors: Xiong
authors: Anaies
authors: A
authors: Nazarians-Armavil
authors: Md
authors: M
authors: Alamgir
authors: Mehrab
authors: M
authors: Ali
authors: Oxana
authors: O
authors: Pogoutse
authors: Asaf
authors: A
authors: Pe'er
authors: Roland
authors: R
authors: Arnold
authors: Magali
authors: M
authors: Michaut
authors: John
authors: J
authors: Parkinson
authors: Ashkan
authors: A
authors: Golshani
authors: Chris
authors: C
authors: Whitfield
authors: Shoshana J
authors: SJ
authors: Wodak
authors: Gabriel
authors: G
authors: Moreno-Hagelsieb
authors: Jack F
authors: JF
authors: Greenblatt
authors: Andrew
authors: A
authors: Emili
mesh_terms: D002462:Cell Membrane / Q000235:genetics*; D003470:Culture Media; D004351:Drug Resistance / Q000235:genetics; D004843:Epistasis, Genetic / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D059647:Gene-Environment Interaction; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D003470:Culture Media; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins