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

• DOI: 10.1371/journal.pgen.1002377
• Publication Date: 2011-11-17T21:35:33Z
• Authors: Mohan Babu; J. Javier Díaz-Mejía; James Vlasblom; Alla Gagarinova; Sadhna Phanse; Chris Graham; Fouad Yousif; Huiming Ding; Xuejian Xiong; Anaies Nazarians-...; Md Alamgir; Mehrab Ali; Oxana Pogoutse; Asaf Pe'er; Roland Arnold; Magali Michaut; John Parkinson; Ashkan Golshani; Chris Whitfield; Shoshana J. Wodak; Gabriel Moreno-Ha...; Jack F. Greenblatt; Andrew Emili
• Keywords: 0301 basic medicine; Cell Membrane; Drug Resistance; Membrane Proteins; Epistasis, Genetic; Molecular Sequence Annotation; Gene Expression Regulation, Bacterial; QH426-470; Culture Media; 3. Good health; Microscopy, Electron; 03 medical and health sciences; Genetics; Escherichia coli; Gene-Environment Interaction; Microtubule-Associated Proteins; Metabolic Networks and Pathways; Research Article; Oligonucleotide Array Sequence Analysis

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.