A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP.
Hisert, Katherine B. 1; MacCoss, Michael 2; Shiloh, Michael U. 1; Darwin, K. Heran 1; Singh, Shaneen 1; Jones, Roger A. 3; Ehrt, Sabine 1; Zhang, Zhaoying 3; Gaffney, Barbara L. 3; Gandotra, Sheetal 1; Holden, David W. 4; Murray, Diana 1; Nathan, Carl 1,*
[Article]
Molecular Microbiology.
56(5):1234-1245, June 2005.
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Summary: 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.
Copyright (C) 2005 Blackwell Publishing Ltd.