Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by physiological and genetic factors modulating the quorum sensing-dependent control pathway
Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by physiological and genetic factors modulating the quorum sensing-dependent control pathway
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DOI：
10.1111/j.1365-2958.2004.04397.x
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发表时间：
2005-01-01
影响因子：
3.6
通讯作者：
Salmond, GPC
中科院分区：
文献类型：
--
作者：
McGowan, SJ;Barnard, AML;Salmond, GPC
胡萝卜Erwinia carotovora产生β -内酰胺类抗生素碳青霉烯，以响应群体感应信号分子N-（3-氧己醇）- l -高丝氨酸内酯（OHHL）。我们已经绘制了第一个生物合成基因carA上游的ohhl依赖启动子。我们还分析了碳青霉烯表达的已知遗传调控因子carR、carI（分别编码LuxR和LuxI的同源物）和hor（编码SlyA/ marr样转录调控因子）对该启动子的影响。我们描述了一个以前未知的位于kara - h操纵子中的启动子。该启动子不响应CarR，并且是carFG基因编码的碳青霉烯类抗性决定因子的群体感应独立表达所必需的。我们绘制了carR、carI和hor转录起始点的图谱，表明在OHHL存在的情况下carR是正向自动调节的，并证明了carI转录受到负反馈的影响。此外，各种环境和生理因素被证明会影响汽车生物合成基因的转录。碳源的性质和生长温度通过调节OHHL信号分子的水平来影响碳青霉烯的产生，从而在生理上微调群体感应调节系统。
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.