Esteves Nathaniel C, Scharf Birgit E
Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA.
Sci Rep. 2024 Jul 31;14(1):17750. doi: 10.1038/s41598-024-68747-3.
Serratia marcescens is an opportunistic human pathogen that produces a vibrant red pigment called prodigiosin. Prodigiosin has implications in virulence of S. marcescens and promising clinical applications. We discovered that addition of the virulent flagellotropic bacteriophage χ (Chi) to a culture of S. marcescens stimulates a greater than fivefold overproduction of prodigiosin. Active phage infection is required for the effect, as a χ-resistant strain lacking flagella does not respond to phage presence. Via a reporter fusion assay, we have determined that the addition of a χ-induced S. marcescens cell lysate to an uninfected culture causes a threefold increase in transcription of the pig operon, containing genes essential for pigment biosynthesis. Replacement of the pig promoter with a constitutive promoter abolished the pigmentation increase, indicating that regulatory elements present in the pig promoter likely mediate the phenomenon. We hypothesize that S. marcescens detects the threat of phage-mediated cell death and reacts by producing prodigiosin as a stress response. Our findings are of clinical significance for two main reasons: (i) elucidating complex phage-host interactions is crucial for development of therapeutic phage treatments, and (ii) overproduction of prodigiosin in response to phage could be exploited for its biosynthesis and use as a pharmaceutical.
粘质沙雷氏菌是一种机会性人类病原体，可产生一种名为灵菌红素的鲜艳红色色素。灵菌红素与粘质沙雷氏菌的毒力有关，并具有良好的临床应用前景。我们发现，向粘质沙雷氏菌培养物中添加毒性嗜鞭毛噬菌体χ（Chi）可刺激灵菌红素的产量增加超过五倍。这种效应需要活跃的噬菌体感染，因为缺乏鞭毛的χ抗性菌株对噬菌体的存在没有反应。通过报告基因融合试验，我们确定向未感染的培养物中添加χ诱导的粘质沙雷氏菌细胞裂解物会导致色素生物合成必需基因所在的pig操纵子的转录增加三倍。用组成型启动子替换pig启动子可消除色素沉着增加，这表明pig启动子中存在的调控元件可能介导了这一现象。我们推测，粘质沙雷氏菌检测到噬菌体介导的细胞死亡威胁，并通过产生灵菌红素作为应激反应做出反应。我们的发现具有临床意义，主要有两个原因：（i）阐明复杂的噬菌体-宿主相互作用对于治疗性噬菌体治疗的开发至关重要，（ii）响应噬菌体而过量产生的灵菌红素可用于其生物合成并用作药物。
