A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP

Mol Microbiol. 2005 Jun;56(5):1234-45. doi: 10.1111/j.1365-2958.2005.04632.x.

Abstract

Signature-tagged transposon mutagenesis of Salmonella with differential recovery from wild-type and immunodeficient mice revealed that the gene here named cdgR[for c-diguanylate (c-diGMP) regulator] is required for the bacterium to resist host phagocyte oxidase in vivo. CdgR consists solely of a glutamate-alanine-leucine (EAL) domain, a predicted cyclic diGMP (c-diGMP) phosphodiesterase. Disruption of cdgR decreased bacterial resistance to hydrogen peroxide and accelerated bacterial killing of macrophages. An ultrasensitive assay revealed c-diGMP in wild-type Salmonella with increased levels in the CdgR-deficient mutant. Thus, besides its known role in regulating cellulose synthesis and biofilm formation, bacterial c-diGMP also regulates host-pathogen interactions involving antioxidant defence and cytotoxicity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • DNA Transposable Elements
  • Hydrogen Peroxide / pharmacology
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Sequence Alignment

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA Transposable Elements
  • bis(3',5')-cyclic diguanylic acid
  • Hydrogen Peroxide
  • Cyclic GMP