GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility.
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.
Microbiology and Tumorbiology Center (MTC), Karolinska Institutet, Box 280, SE-171 77 Stockholm, Sweden.
Roger
R
Simm
Michael
M
Morr
Abdul
A
Kader
Manfred
M
Nimtz
Ute
U
Römling
D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D006090:Gram-Negative Bacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems
D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D010727:Phosphoric Diester Hydrolases; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP