title: A Serratia marcescens PigP homolog controls prodigiosin biosynthesis, swarming motility and hemolysis and is regulated by cAMP-CRP and HexS.
abstract: Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment.
authors.affiliation: Charles T Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Eye Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
authors.forename: Roni M
authors.initials: RM
authors.lastname: Lahr
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Stella
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Arena
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Brothers
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kwak
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kalivoda
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D047630:Depsipeptides / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006461:Hemolysis / Q000187:drug effects; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009068:Movement / Q000187:drug effects; D009154:Mutation; D009876:Operon; D011353:Prodigiosin / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid; D012706:Serratia marcescens / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D047630:Depsipeptides; D008565:Membrane Proteins; D014157:Transcription Factors; C009246:serratamolide; D006602:Hexosyltransferases; C414441:PIGP protein, human; D011353:Prodigiosin