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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.

Original publication

DOI

10.1111/j.1365-2958.2004.04397.x

Type

Journal article

Journal

Mol Microbiol

Publication Date

01/2005

Volume

55

Pages

526 - 545

Keywords

4-Butyrolactone, Bacterial Proteins, Carbapenems, Carbon, Culture Media, Gene Expression Regulation, Bacterial, Operon, Oxygen, Pectobacterium carotovorum, Promoter Regions, Genetic, Signal Transduction, Temperature, Transcription, Genetic