title: A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP.
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.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, and Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Hisert
authors.forename: Michael
authors.initials: M
authors.lastname: MacCoss
authors.forename: Michael U
authors.initials: MU
authors.lastname: Shiloh
authors.forename: K Heran
authors.initials: KH
authors.lastname: Darwin
authors.forename: Shaneen
authors.initials: S
authors.lastname: Singh
authors.forename: Roger A
authors.initials: RA
authors.lastname: Jones
authors.forename: Sabine
authors.initials: S
authors.lastname: Ehrt
authors.forename: Zhaoying
authors.initials: Z
authors.lastname: Zhang
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Gaffney
authors.forename: Sheetal
authors.initials: S
authors.lastname: Gandotra
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
authors.forename: Diana
authors.initials: D
authors.lastname: Murray
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004251:DNA Transposable Elements; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D016415:Sequence Alignment
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C062025:bis(3',5')-cyclic diguanylic acid; D006861:Hydrogen Peroxide; D006152:Cyclic GMP