Lücking Genia, Dommel Monica K, Scherer Siegfried, Fouet Agnes, Ehling-Schulz Monika
Microbial Ecology Group, Department of Biosciences, WZW, Technische Universität München, D-85354 Freising, Germany.
Institut Pasteur, Unité Toxines et Pathogénie Bactérienne, CNRS URA 2172, Paris, France.
Microbiology (Reading). 2009 Mar;155(Pt 3):922-931. doi: 10.1099/mic.0.024125-0.
Cereulide, a depsipeptide structurally related to the antibiotic valinomycin, is responsible for the emetic type of gastrointestinal disease caused by Bacillus cereus. Recently, it has been shown that cereulide is produced non-ribosomally by the plasmid-encoded peptide synthetase Ces. Using deletion mutants of the emetic reference strain B. cereus F4810/72, the influence of the well-known transcription factors PlcR, Spo0A and AbrB on cereulide production and on the transcription of the cereulide synthetase gene cluster was investigated. Our data demonstrate that cereulide synthesis is independent of the B. cereus specific virulence regulator PlcR but belongs to the Spo0A-AbrB regulon. Although cereulide production turned out to be independent of sporulation, it required the activity of the sporulation factor Spo0A. The sigma(A)-promoted transcription of spo0A was found to be crucial for cereulide production, while the sigma(H)-driven transcription of spo0A did not affect cereulide synthesis. Overexpression of the transition state factor AbrB in B. cereus F4810/72 resulted in a non-toxic phenotype. Moreover, AbrB was shown to bind efficiently to the main promoter region of the ces operon, indicating that AbrB acts as a repressor of cereulide production by negatively affecting ces transcription.
蜡样芽胞杆菌呕吐毒素（cereulide）是一种与抗生素缬氨霉素结构相关的环肽，由蜡样芽胞杆菌引起的呕吐型胃肠道疾病与之有关。最近研究表明，蜡样芽胞杆菌呕吐毒素由质粒编码的肽合成酶Ces非核糖体合成。利用呕吐参考菌株蜡样芽胞杆菌F4810/72的缺失突变体，研究了著名的转录因子PlcR、Spo0A和AbrB对蜡样芽胞杆菌呕吐毒素产生及蜡样芽胞杆菌呕吐毒素合成酶基因簇转录的影响。我们的数据表明，蜡样芽胞杆菌呕吐毒素的合成不依赖于蜡样芽胞杆菌特异性毒力调节因子PlcR，而是属于Spo0A-AbrB调节子。虽然蜡样芽胞杆菌呕吐毒素的产生与孢子形成无关，但它需要孢子形成因子Spo0A的活性。发现spo0A由sigma(A)促进的转录对蜡样芽胞杆菌呕吐毒素的产生至关重要，而spo0A由sigma(H)驱动的转录不影响蜡样芽胞杆菌呕吐毒素的合成。在蜡样芽胞杆菌F4810/72中过表达过渡态因子AbrB会导致无毒表型。此外，AbrB被证明能有效结合ces操纵子的主要启动子区域，表明AbrB通过负面影响ces转录而作为蜡样芽胞杆菌呕吐毒素产生的阻遏物。
