title: Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by physiological and genetic factors modulating the quorum sensing-dependent control pathway.
abstract: Erwinia carotovora produces the beta-lactam antibiotic, carbapenem, in response to a quorum sensing signalling molecule, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). We have mapped the OHHL-dependent promoter upstream of the first of the biosynthetic genes, carA. We have also analysed the effect on this promoter of the known genetic regulators of carbapenem expression, carR, carI (encoding homologues of LuxR and LuxI respectively) and hor (encoding a SlyA/MarR-like transcriptional regulator). We describe a previously unknown promoter located within the carA-H operon. This promoter does not respond to CarR and is required for quorum sensing-independent expression of the carbapenem resistance determinants encoded by the carFG genes. We have mapped the carR, carI and hor transcription start points, shown that CarR is positively autoregulated in the presence of OHHL, and have demonstrated negative feedback affecting transcription of carI. In addition, various environmental and physiological factors were shown to impinge on the transcription of the car biosynthetic genes. The nature of the carbon source and the temperature of growth influence carbapenem production by modulating the level of the OHHL signalling molecule, and thereby physiologically fine-tune the quorum sensing regulatory system.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: McGowan
authors.forename: Anne M L
authors.initials: AM
authors.lastname: Barnard
authors.forename: Gulgun
authors.initials: G
authors.lastname: Bosgelmez
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sebaihia
authors.forename: Natalie J L
authors.initials: NJ
authors.lastname: Simpson
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Todd
authors.forename: Martin
authors.initials: M
authors.lastname: Welch
authors.forename: Neil A
authors.initials: NA
authors.lastname: Whitehead
authors.forename: George P C
authors.initials: GP
authors.lastname: Salmond
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015780:Carbapenems / Q000096:biosynthesis*; D002244:Carbon / Q000378:metabolism; D003470:Culture Media; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D010100:Oxygen / Q000494:pharmacology; D016973:Pectobacterium carotovorum / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; C091096:CarR protein, Azospirillum brasilense; D015780:Carbapenems; D003470:Culture Media; C088386:homoserine lactone; D002244:Carbon; D015107:4-Butyrolactone; D010100:Oxygen