Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

TitleGenetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.
Publication TypeJournal Article
Year of Publication2011
AuthorsBabu, M., J. J Díaz-Mejía, J. Vlasblom, A. Gagarinova, S. Phanse, C. Graham, F. Yousif, H. Ding, X. Xiong, A. Nazarians-Armavil, M. Alamgir, M. Ali, O. Pogoutse, A. Pe'er, R. Arnold, M. Michaut, J. Parkinson, A. Golshani, C. Whitfield, S. J. Wodak, G. Moreno-Hagelsieb, J. F. Greenblatt, and A. Emili
JournalPLoS Genet
Volume7
Issue11
Paginatione1002377
Date Published2011 Nov
ISSN1553-7404
KeywordsCell Membrane, Culture Media, Drug Resistance, Epistasis, Genetic, Escherichia coli, Gene Expression Regulation, Bacterial, Gene-Environment Interaction, Membrane Proteins, Metabolic Networks and Pathways, Microscopy, Electron, Microtubule-Associated Proteins, Molecular Sequence Annotation, Oligonucleotide Array Sequence Analysis
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.

DOI10.1371/journal.pgen.1002377
Alternate JournalPLoS Genet.
PubMed ID22125496
PubMed Central IDPMC3219608
Grant ListMOP-82852 / / Canadian Institutes of Health Research / Canada
MOP-82940 / / Canadian Institutes of Health Research / Canada