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- Title
Carbapenem antibiotic biosynthesis inErwinia carotovorais regulated by physiological and genetic factors modulating the quorum sensing-dependent control pathway.
- Authors
McGowan, Simon J.; Barnard, Anne M. L.; Bosgelmez, Gulgun; Sebaihia, Mohammed; Simpson, Natalie J. L.; Thomson, Nicholas R.; Todd, Daniel E.; Welch, Martin; Whitehead, Neil A.; Salmond, George P. C.
- Abstract
Erwinia carotovoraproduces theβ-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) andhor(encoding a SlyA/MarR-like transcriptional regulator). We describe a previously unknown promoter located within thecarA-Hoperon. This promoter does not respond to CarR and is required for quorum sensing-independent expression of the carbapenem resistance determinants encoded by thecarFGgenes. We have mapped thecarR,carIandhortranscription start points, shown that CarR is positively autoregulated in the presence of OHHL, and have demonstrated negative feedback affecting transcription ofcarI. In addition, various environmental and physiological factors were shown to impinge on the transcription of thecarbiosynthetic 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.
- Subjects
BIOCHEMISTRY; ENTEROBACTERIACEAE; BETA lactam antibiotics; GENETIC transcription; GENETIC code; BIOTECHNOLOGY
- Publication
Molecular Microbiology, 2005, Vol 55, Issue 2, p526
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/j.1365-2958.2004.04397.x