GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility

Mol Microbiol. 2004 Aug;53(4):1123-34. doi: 10.1111/j.1365-2958.2004.04206.x.


Cyclic nucleotides represent second messenger molecules in all kingdoms of life. In bacteria, mass sequencing of genomes detected the highly abundant protein domains GGDEF and EAL. We show here that the GGDEF and EAL domains are involved in the turnover of cyclic-di-GMP (c-di-GMP) in vivo whereby the GGDEF domain stimulates c-di-GMP production and the EAL domain c-di-GMP degradation. Thus, most probably, GGDEF domains function as c-di-GMP cyclase and EAL domains as phosphdiesterase. We further show that, in the pathogenic organism Salmonella enterica serovar Typhimurium, the nosocomial pathogen Pseudomonas aeruginosa and the commensal species Escherichia coli, GGDEF and EAL domains mediate similar phenotypic changes related to the transition between sessility and motility. Thus, the data suggest that c-di-GMP is a novel global second messenger in bacteria the metabolism of which is controlled by GGDEF and EAL domain proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli / physiology
  • Escherichia coli Proteins
  • Gene Expression Regulation, Bacterial*
  • Gram-Negative Bacteria / enzymology
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / metabolism
  • Gram-Negative Bacteria / physiology*
  • Humans
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / metabolism*
  • Phosphorus-Oxygen Lyases / chemistry
  • Phosphorus-Oxygen Lyases / metabolism*
  • Protein Structure, Tertiary*
  • Pseudomonas aeruginosa / chemistry
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / physiology
  • Salmonella typhimurium / chemistry
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / physiology
  • Second Messenger Systems


  • Escherichia coli Proteins
  • bis(3',5')-cyclic diguanylic acid
  • Phosphoric Diester Hydrolases
  • Phosphorus-Oxygen Lyases
  • diguanylate cyclase
  • Cyclic GMP