Resistance to serine in Bacillus subtilis: identification of the serine transporter YbeC and of a metabolic network that links serine and threonine metabolism

Environ Microbiol. 2020 Sep;22(9):3937-3949. doi: 10.1111/1462-2920.15179. Epub 2020 Aug 13.


The Gram-positive bacterium Bacillus subtilis uses serine not only as a building block for proteins but also as an important precursor in many anabolic reactions. Moreover, a lack of serine results in the initiation of biofilm formation. However, excess serine inhibits the growth of B. subtilis. To unravel the underlying mechanisms, we isolated suppressor mutants that can tolerate toxic serine concentrations by three targeted and non-targeted genome-wide screens. All screens as well as genetic complementation in Escherichia coli identified the so far uncharacterized permease YbeC as the major serine transporter of B. subtilis. In addition to YbeC, the threonine transporters BcaP and YbxG make minor contributions to serine uptake. A strain lacking these three transporters was able to tolerate 100 mM serine whereas the wild type strain was already inhibited by 1 mM of the amino acid. The screen for serine-resistant mutants also identified mutations that result in increased serine degradation and in increased expression of threonine biosynthetic enzymes suggesting that serine toxicity results from interference with threonine biosynthesis.

Publication types

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

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism*
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Metabolic Networks and Pathways*
  • Mutation
  • Serine / metabolism*
  • Serine / pharmacology
  • Threonine / genetics
  • Threonine / metabolism*


  • Amino Acid Transport Systems
  • Bacterial Proteins
  • Threonine
  • Serine