PMID:21183666

Citation	Hantke, K, Winkler, K and Schultz, JE (2011) Escherichia coli exports cyclic AMP via TolC. J. Bacteriol. 193:1086-9
Abstract	In Escherichia coli more than 180 genes are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made by intracellular adenylyl cyclases is found in the culture medium. How is cAMP exported from E. coli? In a tolC mutant, 0.03 mM IPTG (isopropyl-β-d-thiogalactopyranoside) was sufficient to induce β-galactosidase compared to 0.1 mM IPTG in the parent strain. In a cya mutant unable to produce cAMP about 1 mM extracellular cAMP was required to induce β-galactosidase, whereas in a cya tolC mutant 0.1 mM cAMP was sufficient. When cAMP in E. coli cya was generated intracellularly by a recombinant, weakly active adenylyl cyclase from Corynebacterium glutamicum, the critical level of cAMP necessary for induction of maltose degradation was only achieved in a tolC mutant and not in the parent strain. Deletion of a putative cAMP phosphodiesterase of E. coli, CpdA, resulted in a slightly similar, yet more diffuse phenotype. The data demonstrate that export of cAMP via TolC is a most efficient way of E. coli to lower high concentrations of cAMP in the cell and maintain its sensitivity in changing metabolic environments.
Links	PubMed PMC3067598 Online version:10.1128/JB.01399-10
Keywords	Bacterial Outer Membrane Proteins/genetics; Bacterial Outer Membrane Proteins/metabolism; Base Sequence; Biological Transport; Chromosome Mapping; Chromosomes, Bacterial; Cyclic AMP/metabolism; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Deletion; Gene Expression Regulation, Bacterial/physiology; Membrane Transport Proteins/genetics; Membrane Transport Proteins/metabolism; Molecular Sequence Data; Mutation
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECOLI:TOLC		GO:0071320: cellular response to cAMP	ECO:0000315:		P		FIG. 1. IPTG concentration response curves for β-galactosidase induction in E. coli. The strains HfrC ({blacklozenge}) and the HfrC tolC ({blacksquare}) mutant were induced for 75 min, and the β-galactosidase activity was determined. FIG. 3. cAMP concentration response curves for β-galactosidase induction in E. coli. Strains BTH2 cya ({blacklozenge}), H41 cya tolC ({blacksquare}), and H74 cya cpdA ({blacktriangleup}) were grown in LB medium to an OD600 of about 1.2, diluted 10-fold, and induced with 1 mM IPTG. After 75 min, the β-galactosidase activity was determined.	complete

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