Hisert, K. B. et al. A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP. Mol. Microbiol. 56, 1234-1245

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.
Molecular Microbiology (Impact Factor: 4.42). 07/2005; 56(5):1234-45. DOI: 10.1111/j.1365-2958.2005.04632.x
Source: PubMed


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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    • "For instance, cellulose synthesis is affected by cyclic di-GMP levels in Gluconacetobacter xylinus (Ross et al., 1987), and biofilm formation and motility in Pseudomonas aeruginosa are regulated by cyclic di-GMP levels (Hickman et al., 2005). In both Vibrio cholerae (Tischler and Camilli, 2004) and Salmonella enterica serovar Typhimurium (Hisert et al., 2005), reduction of cyclic di-GMP concentration results in the induction of virulence genes. Cyclic di-GMP has also been shown to interact directly with riboswitch Cd1, where a decrease in cyclic di-GMP concentration increases the level of translation of the downstream flagella operon (Sudarsan et al., 2008). "
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    Structure 02/2012; 20(2):350-63. DOI:10.1016/j.str.2012.01.003 · 5.62 Impact Factor
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    • "On the contrary, in a S. enteriditis strain with deletion of all GG(D/E)EF domain proteins, expression of the catalytically inactive di-guanylate cyclase STM4551 was sufficient to restore virulence in the typhoid fever mouse model, a systemic infection model [26]. Also the EAL-domain like protein STM1344, which prevents Salmonella induced macrophage killing and mediates resistance to oxidative stress [25], neither metabolizes nor binds c-di-GMP [13]. In contrast, c-di-GMP signaling has been shown to modulate virulence in the enteric pathogen Vibrio cholerae, the causative agent of cholera [27]. "
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    • "Cyclic di-GMP signalling can affect virtually almost all kind of virulence phenotypes including the overall in vivo virulence phenotype in animals and plants (Kulesekara et al., 2006; Ryan et al., 2007; Tamayo et al., 2007). Individual phenotypes, for example, interactions with host cells such as adherence to host cells, host cell invasion, cytotoxicity, intracellular infection, secretion of virulence factors and stimulation of immune response have been reported to be affected by cyclic di-GMP signalling (Hisert et al., 2005; Tischler and Camilli, 2005; Kulesekara et al., 2006; Lai et al., 2008; McWhirter et al., 2009; Kumagai et al., 2010; Lee et al., 2010a; Lamprokostopoulou et al., 2010; Sauer et al., 2011). Based on early investigations, the common view is that an acute infection process does not require cyclic di-GMP (Tamayo et al., 2007). "
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