Monday, August 2, 2010
Pacific Concourse (Hyatt Regency San Francisco)
Neil Williamson1, Josh Ramsay
1, Peter Fineran
2, Kathryn Lilley
3 and George Salmond
1, (1)Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom, (2)Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand, (3)Cambridge Centre for Proteomics, Cambridge System Biology Centre, University of Cambridge, Cambridge, United Kingdom
Serratia are
opportunistic human, plant and insect pathogens, and are members of the Enterobacteriacae.
Serratia sp. ATCC 39006 (
Serratia 39006) secretes pectinases and cellulases and a RhlA-dependent surfactant which facilitates bacterial swarming.
Serratia 39006 produces the secondary metabolites, carbapenem a simple b-lactam and a red pigmented linear tripyrrolic antibiotic, prodigiosin. Prodigiosin has numerous biological properties including antifungal, antibacterial, antiprotazoal, immunosuppressive and anticancer activities. Prodigiosin is currently attracting a great deal of interest as a potential anticancer agent with a synthetic derivative of undecylprodigiosin (Obatoclax) currently in phase I/II clinical trials in single and dual agent studies to treat multiple forms of cancer.
In Serratia 39006 a complex regulatory hierarchy requiring multiple genetic and environmental inputs controls antibiotic production, swarming and virulence. Antibiotic production in Serratia 39006 is regulated by a SmaIR dependent AHL-based quorum sensing (QS) system, the GacA/rsm (repressor of secondary metabolism) system, rap (regulator of antibiotic and pigment production) and a “master” regulator, PigP.
In this study, we have used the non-gel based approach isobaric tags for relative and absolute quantification (ITRAQ) to perform a comparative proteomics study of the key global regulators of antibiotic production in Serratia 39006. We also investigate a novel regulator of prodigiosin and surfactant production, which we have termed RsmS. The results of this study have provided not only valuable insights into the regulation of prodigiosin and carbapenem in Serratia 39006 but have revealed previously unidentified cryptic clusters.
