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

doi:10.1111/j.1365-2958.2005.04632.x

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 journal › Article › peer-review

119 Scopus citations

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 language	English (US)
Pages (from-to)	1234-1245
Number of pages	12
Journal	Molecular Microbiology
Volume	56
Issue number	5
DOIs	https://doi.org/10.1111/j.1365-2958.2005.04632.x
State	Published - Jun 2005

ASJC Scopus subject areas

Microbiology
Molecular Biology

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10.1111/j.1365-2958.2005.04632.x

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Hisert, K. B., MacCoss, M., Shiloh, M. U., Darwin, K. H., Singh, S., Jones, R. A., Ehrt, S., Zhang, Z., Gaffney, B. L., Gandotra, S., Holden, D. W., 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, 56(5), 1234-1245. https://doi.org/10.1111/j.1365-2958.2005.04632.x

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

Research output: Contribution to journal › Article › peer-review

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

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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.",

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AU - Darwin, K. Heran

AU - Singh, Shaneen

AU - Jones, Roger A.

AU - Ehrt, Sabine

AU - Zhang, Zhaoying

AU - Gaffney, Barbara L.

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AU - Holden, David W.

AU - Murray, Diana

AU - Nathan, Carl

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AB - 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.

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

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