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

PLoS Genet. 2011 Nov;7(11):e1002377. doi: 10.1371/journal.pgen.1002377. Epub 2011 Nov 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / genetics*
  • Culture Media
  • Drug Resistance / genetics
  • Epistasis, Genetic / genetics*
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Gene Expression Regulation, Bacterial
  • Gene-Environment Interaction
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Metabolic Networks and Pathways / genetics
  • Microscopy, Electron
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Annotation
  • Oligonucleotide Array Sequence Analysis


  • Culture Media
  • Membrane Proteins
  • Microtubule-Associated Proteins