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

Research output: Contribution to journalArticle

Authors

  • Mohan Babu
  • J Javier Díaz-Mejía
  • James Vlasblom
  • Alla Gagarinova
  • Sadhna Phanse
  • Chris Graham
  • Fouad Yousif
  • Huiming Ding
  • Xuejian Xiong
  • Anaies Nazarians-Armavil
  • Md Alamgir
  • Mehrab Ali
  • Oxana Pogoutse
  • Asaf Pe'er
  • Magali Michaut
  • John Parkinson
  • Ashkan Golshani
  • Chris Whitfield
  • Shoshana J Wodak
  • Gabriel Moreno-Hagelsieb
  • Jack F Greenblatt
  • Andrew Emili

Colleges, School and Institutes

External organisations

  • Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Canada. mohan.babu@utoronto.ca

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.

Details

Original languageEnglish
Pages (from-to)e1002377
JournalPLoS Genetics
Volume7
Issue number11
Publication statusPublished - Nov 2011

Keywords

  • Cell 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, Journal Article, Research Support, Non-U.S. Gov't