Chemical conditionality: A genetic strategy to probe organelle assembly

Natividad Ruiz, Brian Falcone, Daniel Kahne, Thomas J. Silhavy

Research output: Contribution to journalArticlepeer-review

246 Scopus citations


The assembly of the Escherichia coli outer membrane (OM) is poorly understood. Although insight into fundamental cellular processes is often obtained from studying mutants, OM-defective mutants have not been very informative because they generally have nonspecific permeability defects. Here we show that toxic small molecules can be used in selections employing strains with permeability defects to create particular chemical conditions that demand specific suppressor mutations. Suppressor phenotypes are correlated with the physical properties of the small molecules, but the mutations are not in their target genes. Instead, mutations allow survival by partially restoring membrane impermeability. Using "chemical conditionality," we identified mutations in yfgL, and, here and in the accompanying paper by Wu et al. published in this issue of Cell (Wu et al., 2005), we show that YfgL is part of a multiprotein complex involved in the assembly of OM β barrel proteins. We posit that panels of toxic small molecules will be useful for generating chemical conditionalities that enable identification of genes required for organelle assembly in other organisms.

Original languageEnglish (US)
Pages (from-to)307-317
Number of pages11
Issue number2
StatePublished - Apr 22 2005

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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