Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules.
Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules.
复制标题
Serratia次生代谢产物蛋白质通过产生损害生物分子的活性氧来抑制铜绿假单胞菌生物膜的发育。
DOI：
10.3389/fmicb.2016.00972
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发表时间：
2016
影响因子：
5.2
通讯作者：
Manefield M
中科院分区：
文献类型：
--
作者：
Kimyon Ö;Das T;Ibugo AI;Kutty SK;Ho KK;Tebben J;Kumar N;Manefield M
灵菌红是一种杂环细菌次级代谢产物，属于三吡咯化合物类，由包括沙雷氏菌在内的多种细菌合成。灵菌红在过去十年中因其诱导多种癌细胞系凋亡的能力而成为深入研究的主题。报告表明，在铜离子存在的情况下，灵菌红会促进双链 DNA (dsDNA) 的氧化损伤，从而抑制细胞周期进程和细胞死亡。然而，此前并未发现灵菌红与生物膜抑制有关。在这项研究中，提出了灵菌红和通过氧化还原活性代谢物的产生来抑制生物膜之间的联系。我们的研究表明，灵菌红素 (500 μM)（从粘质沙雷氏菌培养物中提取）和灵菌红素/铜 (II)（各 100 μM）复合物具有很强的 RNA 和 dsDNA 切割特性，但对蛋白质没有明显影响。结果支持 H2O2 和羟基自由基的产生对生物分子造成氧化损伤。此外，还证明活性氧清除剂显着降低了灵菌红的 DNA 和 RNA 切割性能。由于灵菌红或灵菌红/铜(II)复合物对核酸的裂解，铜绿假单胞菌细胞表面疏水性和生物膜完整性发生显着改变。此外，灵菌红还促进了杀菌活性。灵菌素引起核酸降解的能力为干扰细胞外 DNA 依赖性细菌生物膜提供了新的机会。
Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms.