A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP
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.
Document Type: Research Article
Affiliations: 1: Department of Genome Sciences, University of Washington, Seattle, WA, USA. 2: Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA. 3: Center for Molecular Microbiology and Infection, Imperial College, London, UK.
Publication date: June 1, 2005