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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

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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    • "More than 40 can be found in Pseudomonas aeruginosa, which raises the question of whether these enzymes are redundant, have specific roles or targets, or are associated with specific environmental conditions. The role of c-di-GMP in pathogenesis has been extensively studied in a number of animal and human bacterial pathogens, including Salmonella enterica (Hisert et al., 2005; Lamprokostopoulou et al., 2010), Vibrio cholerae (Tischler and Camilli, 2005), Yersinia pestis (Bobrov et al., 2011; 2014) and P. aeruginosa (Kulasakara et al., 2006; Ryan et al., 2009; Li et al., 2014). Pseudomonas aeruginosa is a versatile Gram-negative bacterium that can be found in various environments, including soil, water and vegetation (Lyczak et al., 2000). "
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    No preview · Article · Mar 2015 · Environmental Microbiology
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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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    • "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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