Romanowski Eric G, Lehner Kara M, Martin Natalie C, Patel Kriya R, Callaghan Jake D, Stella Nicholas A, Shanks Robert M Q
Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh , Pittsburgh PA.
Pol J Microbiol. 2019;68(1):43-50. doi: 10.21307/pjm-2019-005.
Several biotypes of the Gram-negative bacterium produce the tri-pyrole pigment and secondary metabolite prodigiosin. The biological activities of this pigment have therapeutic potential. For over half a century it has been known that biosynthesis of prodi giosin is inhibited when bacteria are grown at elevated temperatures, yet the fundamental mechanism underlying this thermoregulation has not been characterized. In this study, chromosomal and plasmid-borne transcriptional reporters revealed reduced transcription of the prodigiosin biosynthetic operon at 37°C compared to 30°C indicating transcriptional control of pigment production. Moreover, induced expression of the prodigiosin biosynthetic operon at 37°C was able to produce pigmented colonies and cultures demonstrating that physiological conditions at 37°C allow prodigiosin production and indicating that post-transcriptional control is not a major contributor to the thermoregulation of prodigiosin pigmentation. Genetic experiments support the model that the HexS transcription factor is a key contributor to thermoregulation of pigmentation, whereas CRP plays a minor role, and a clear role for EepR and PigP was not observed. Together, these data indicate that thermoregulation of prodigiosin production at elevated temperatures is controlled largely, if not exclusively, at the transcriptional level. Several biotypes of the Gram-negative bacterium produce the tri-pyrole pigment and secondary metabolite prodigiosin. The biological activities of this pigment have therapeutic potential. For over half a century it has been known that biosynthesis of prodi giosin is inhibited when bacteria are grown at elevated temperatures, yet the fundamental mechanism underlying this thermoregulation has not been characterized. In this study, chromosomal and plasmid-borne transcriptional reporters revealed reduced transcription of the prodigiosin biosynthetic operon at 37°C compared to 30°C indicating transcriptional control of pigment production. Moreover, induced expression of the prodigiosin biosynthetic operon at 37°C was able to produce pigmented colonies and cultures demonstrating that physiological conditions at 37°C allow prodigiosin production and indicating that post-transcriptional control is not a major contributor to the thermoregulation of prodigiosin pigmentation. Genetic experiments support the model that the HexS transcription factor is a key contributor to thermoregulation of pigmentation, whereas CRP plays a minor role, and a clear role for EepR and PigP was not observed. Together, these data indicate that thermoregulation of prodigiosin production at elevated temperatures is controlled largely, if not exclusively, at the transcriptional level.
几种革兰氏阴性细菌的生物型可产生三吡咯色素和次级代谢产物灵菌红素。这种色素的生物活性具有治疗潜力。半个多世纪以来，人们已经知道，当细菌在高温下生长时，灵菌红素的生物合成会受到抑制，然而这种温度调节的基本机制尚未得到阐明。在本研究中，染色体和质粒携带的转录报告基因显示，与30°C相比，在37°C时灵菌红素生物合成操纵子的转录减少，这表明色素产生受到转录控制。此外，在37°C诱导灵菌红素生物合成操纵子的表达能够产生有色菌落和培养物，这表明37°C的生理条件允许灵菌红素的产生，并表明转录后控制不是灵菌红素色素沉着温度调节的主要因素。遗传实验支持这样的模型，即HexS转录因子是色素沉着温度调节的关键因素，而CRP起次要作用，未观察到EepR和PigP有明显作用。总之，这些数据表明，在高温下灵菌红素产生的温度调节在很大程度上（如果不是唯一的话）是在转录水平上控制的。几种革兰氏阴性细菌的生物型可产生三吡咯色素和次级代谢产物灵菌红素。这种色素的生物活性具有治疗潜力。半个多世纪以来，人们已经知道，当细菌在高温下生长时，灵菌红素的生物合成会受到抑制，然而这种温度调节的基本机制尚未得到阐明。在本研究中，染色体和质粒携带的转录报告基因显示，与30°C相比，在37°C时灵菌红素生物合成操纵子的转录减少，这表明色素产生受到转录控制。此外，在37°C诱导灵菌红素生物合成操纵子的表达能够产生有色菌落和培养物，这表明37°C的生理条件允许灵菌红素的产生，并表明转录后控制不是灵菌红素色素沉着温度调节的主要因素。遗传实验支持这样的模型，即HexS转录因子是色素沉着温度调节的关键因素，而CRP起次要作用，未观察到EepR和PigP有明显作用。总之，这些数据表明，在高温下灵菌红素产生的温度调节在很大程度上（如果不是唯一的话）是在转录水平上控制的。
