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

Katherine B. Hisert, Michael MacCoss, Michael U. Shiloh, K. Heran Darwin, Shaneen Singh, Roger A. Jones, Sabine Ehrt, Zhaoying Zhang, Barbara L. Gaffney, Sheetal Gandotra, David W. Holden, Diana Murray, Carl Nathan

Research output: Contribution to journalArticle

105 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1234-1245
Number of pages12
JournalMolecular Microbiology
Volume56
Issue number5
DOIs
StatePublished - Jun 2005

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Leucine
Salmonella
Alanine
Glutamic Acid
Antioxidants
Macrophages
Host-Pathogen Interactions
Phosphoric Diester Hydrolases
Phagocytes
Biofilms
Cellulose
Mutagenesis
Hydrogen Peroxide
Oxidoreductases
Bacteria
Genes
Protein Domains

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

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.; MacCoss, Michael; Shiloh, Michael U.; Darwin, K. Heran; Singh, Shaneen; Jones, Roger A.; Ehrt, Sabine; Zhang, Zhaoying; Gaffney, Barbara L.; Gandotra, Sheetal; Holden, David W.; Murray, Diana; Nathan, Carl.

In: Molecular Microbiology, Vol. 56, No. 5, 06.2005, p. 1234-1245.

Research output: Contribution to journalArticle

Hisert, KB, MacCoss, M, Shiloh, MU, Darwin, KH, Singh, S, Jones, RA, Ehrt, S, Zhang, Z, Gaffney, BL, Gandotra, S, Holden, DW, Murray, D & Nathan, C 2005, 'A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: Role of cyclic diGMP', Molecular Microbiology, vol. 56, no. 5, pp. 1234-1245. https://doi.org/10.1111/j.1365-2958.2005.04632.x
Hisert, Katherine B. ; MacCoss, Michael ; Shiloh, Michael U. ; Darwin, K. Heran ; Singh, Shaneen ; Jones, Roger A. ; Ehrt, Sabine ; Zhang, Zhaoying ; Gaffney, Barbara L. ; Gandotra, Sheetal ; Holden, David W. ; Murray, Diana ; Nathan, Carl. / A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages : Role of cyclic diGMP. In: Molecular Microbiology. 2005 ; Vol. 56, No. 5. pp. 1234-1245.
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