Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Eye Center, Pittsburgh, PA 15213, USA.
Res Microbiol. 2010 Mar;161(2):158-67. doi: 10.1016/j.resmic.2009.12.004. Epub 2010 Jan 4.
Many Serratia marcescens strains produce the red pigment prodigiosin, which has antimicrobial and anti-tumor properties. Previous reports suggest that cyclic AMP (cAMP) is a positive regulator of prodigiosin production. Supporting this model, the addition of glucose to growth medium inhibited pigment production in rich and minimal media. Unexpectedly, we observed highly elevated levels of prodigiosin production in isogenic strains with mutations in genes involved in cAMP production (cyaA and crr) and in cAMP-dependent transcriptional signaling (crp). Multicopy expression of the Escherichia coli cAMP-phosphodiesterase gene, cpdA, also conferred a striking increase in prodigiosin production. Exogenous cAMP decreased both pigment production and pigA-lacZ transcription in the wild-type (WT) strain, and pigA-lacZ transcription was significantly increased in a crp mutant relative to WT. Suppressor and epistasis analysis indicate that the hyperpigment phenotype was dependent upon pigment biosynthetic genes (pigA, pigB, pigC, pigD and pigM). These experiments establish cAMP as a negative regulator of prodigiosin production in S. marcescens.
许多粘质沙雷氏菌菌株产生红色色素灵菌红素，具有抗菌和抗肿瘤特性。先前的报告表明，环腺苷酸 (cAMP) 是灵菌红素产生的正调节剂。支持该模型，在丰富和最低培养基中添加葡萄糖抑制了色素的产生。出乎意料的是，我们在涉及 cAMP 产生（cyaA 和 crr）和 cAMP 依赖的转录信号（crp）的基因发生突变的同基因菌株中观察到灵菌红素产量的高度升高。大肠杆菌 cAMP 磷酸二酯酶基因 cpdA 的多拷贝表达也赋予了灵菌红素产量的显著增加。外源 cAMP 降低了野生型 (WT) 菌株中色素的产生和 pigA-lacZ 转录，并且相对于 WT，CRP 突变体中 pigA-lacZ 转录显著增加。抑制子和上位性分析表明，高色素表型依赖于色素生物合成基因（pigA、pigB、pigC、pigD 和 pigM）。这些实验确立了 cAMP 是粘质沙雷氏菌灵菌红素产生的负调节剂。
