Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli

Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):E2561-8. doi: 10.1073/pnas.1209742109. Epub 2012 Aug 20.

Abstract

Cell size varies greatly among different types of cells, but the range in size that a specific cell type can reach is limited. A long-standing question in biology is how cells control their size. Escherichia coli adjusts size and growth rate according to the availability of nutrients so that it grows larger and faster in nutrient-rich media than in nutrient-poor media. Here, we describe how, using classical genetics, we have isolated a remarkably small E. coli mutant that has undergone a 70% reduction in cell volume with respect to wild type. This mutant lacks FabH, an enzyme involved in fatty acid biosynthesis that previously was thought to be essential for the viability of E. coli. We demonstrate that although FabH is not essential in wild-type E. coli, it is essential in cells that are defective in the production of the small-molecule and global regulator ppGpp. Furthermore, we have found that the loss of FabH causes a reduction in the rate of envelope growth and renders cells unable to regulate cell size properly in response to nutrient excess. Therefore we propose a model in which fatty acid biosynthesis plays a central role in regulating the size of E. coli cells in response to nutrient availability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
  • Acetyl-CoA Carboxylase / metabolism
  • Acetyltransferases / metabolism
  • Alleles
  • Anti-Bacterial Agents / pharmacology
  • Cell Membrane / metabolism
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism
  • Fatty Acid Synthase, Type II / metabolism
  • Fatty Acids / metabolism*
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / metabolism
  • Models, Biological
  • Models, Genetic
  • Pyrophosphatases / metabolism
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Fatty Acids
  • Lipopolysaccharides
  • Acetyltransferases
  • fabH protein, E coli
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
  • guanosine-3',5'-bis(diphosphate) 3'-pyrophosphatase
  • Pyrophosphatases
  • Fatty Acid Synthase, Type II
  • Acetyl-CoA Carboxylase
  • accD protein, E coli