title: Cyclic AMP negatively regulates prodigiosin production by Serratia marcescens.
abstract: Many Serratia marcescens strains produce the red pigment prodigiosin, which has antimicrobial and anti-tumor properties. Previous reports suggest that cyclic AMP (cAMP) is a positive regulator of prodigiosin production. Supporting this model, the addition of glucose to growth medium inhibited pigment production in rich and minimal media. Unexpectedly, we observed highly elevated levels of prodigiosin production in isogenic strains with mutations in genes involved in cAMP production (cyaA and crr) and in cAMP-dependent transcriptional signaling (crp). Multicopy expression of the Escherichia coli cAMP-phosphodiesterase gene, cpdA, also conferred a striking increase in prodigiosin production. Exogenous cAMP decreased both pigment production and pigA-lacZ transcription in the wild-type (WT) strain, and pigA-lacZ transcription was significantly increased in a crp mutant relative to WT. Suppressor and epistasis analysis indicate that the hyperpigment phenotype was dependent upon pigment biosynthetic genes (pigA, pigB, pigC, pigD and pigM). These experiments establish cAMP as a negative regulator of prodigiosin production in S. marcescens.
authors.affiliation: Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Eye Center, Pittsburgh, PA 15213, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kalivoda
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Stella
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Aston
authors.forename: James E
authors.initials: JE
authors.lastname: Fender
authors.forename: Paul P
authors.initials: PP
authors.lastname: Thompson
authors.forename: Regis P
authors.initials: RP
authors.lastname: Kowalski
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D003470:Culture Media / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D011353:Prodigiosin / Q000096:biosynthesis*; D012706:Serratia marcescens / Q000378:metabolism / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D000242:Cyclic AMP; D005947:Glucose; D011353:Prodigiosin