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

TitleA glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP.
Publication TypeJournal Article
Year of Publication2005
AuthorsHisert KB, MacCoss M, Shiloh MU, K Darwin H, Singh S, Jones RA, Ehrt S, Zhang Z, Gaffney BL, Gandotra S, Holden DW, Murray D, Nathan C
JournalMol Microbiol
Volume56
Issue5
Pagination1234-45
Date Published2005 Jun
ISSN0950-382X
KeywordsAmino Acid Sequence, Animals, Anti-Bacterial Agents, Bacterial Proteins, Cyclic GMP, DNA Transposable Elements, Hydrogen Peroxide, Macrophages, Mice, Molecular Sequence Data, Mutagenesis, Insertional, Salmonella typhimurium, Sequence Alignment
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.

DOI10.1111/j.1365-2958.2005.04632.x
Alternate JournalMol Microbiol
PubMed ID15882417
Grant ListEB002809 / EB / NIBIB NIH HHS / United States
GM07739 / GM / NIGMS NIH HHS / United States
HL61241 / HL / NHLBI NIH HHS / United States

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