The Listeria monocytogenes Fur-regulated virulence protein FrvA is an Fe(II) efflux P1B4 -type ATPase

Mol Microbiol. 2016 Jun;100(6):1066-79. doi: 10.1111/mmi.13368. Epub 2016 Apr 14.

Abstract

Listeria monocytogenes FrvA (Lmo0641) is critical for virulence in the mouse model and is an ortholog of the Bacillus subtilis Fur- and PerR-regulated Fe(II) efflux P1B4 -type ATPase PfeT. Previously, FrvA was suggested to protect against heme toxicity. Here, we demonstrate that an frvA mutant is sensitive to iron intoxication, but not to other metals. Expression of frvA is induced by high iron and this induction requires Fur. FrvA functions in vitro as a divalent cation specific ATPase most strongly activated by ferrous iron. When expressed in B. subtilis, FrvA increases resistance to iron both in wild-type and in a pfeT null strain. FrvA is a high affinity Fe(II) exporter and its induction imposes severe iron limitation in B. subtilis resulting in derepression of both Fur- and PerR-regulated genes. FrvA also recognizes Co(II) and Zn(II) as substrates and can complement B. subtilis strains defective in the endogenous export systems for these cations. Building on these results, we conclude that FrvA functions in the efflux of Fe(II), and not heme during listerial infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Bacillus subtilis / enzymology
  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Ferrous Compounds / metabolism*
  • Ferrous Compounds / toxicity
  • Gene Expression Regulation, Bacterial
  • Listeria monocytogenes / drug effects
  • Listeria monocytogenes / enzymology
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / metabolism*
  • Mutation
  • Phosphoenolpyruvate Sugar Phosphotransferase System / genetics
  • Phosphoenolpyruvate Sugar Phosphotransferase System / metabolism
  • Repressor Proteins / metabolism
  • Virulence
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Bacterial Proteins
  • Ferrous Compounds
  • Repressor Proteins
  • Virulence Factors
  • Phosphoenolpyruvate Sugar Phosphotransferase System
  • Adenosine Triphosphatases