The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.
The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.
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DOI：
10.3389/fmicb.2015.00137
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发表时间：
2015
影响因子：
5.2
通讯作者：
Salmond GP
中科院分区：
文献类型：
--
作者：
Hellberg JE;Matilla MA;Salmond GP
土壤细菌能够大量产生具有经济和临床重要性的次生代谢产物及其他生物活性化合物。这些天然产物通常由大型多酶复合物合成，如聚酮合酶（PKSs）或非核糖体肽合成酶（NRPSs）。与植物相关的革兰氏阴性菌——普城沙雷氏菌A153能产生多种次生代谢产物，并且能够杀死秀丽隐杆线虫，而秀丽隐杆线虫是研究细菌毒力常用的模式生物。在本研究中，我们发现破坏PKS/NRPS杂合玉米赤霉烯酮（zmn）基因簇会导致对秀丽隐杆线虫“快速致死”能力的减弱，这表明玉米赤霉烯酮具有杀线虫活性。秀丽隐杆线虫对玉米赤霉烯酮的敏感性还呈现出年龄依赖性，较年轻的线虫对这种生物活性分子最为敏感。zmn基因簇在沙雷氏菌属和植物致病性的迪基氏菌属中广泛分布，对携带zmn基因簇菌株的研究表明，其中一些菌株对秀丽隐杆线虫具有很强的毒力。玉米赤霉烯酮此前被描述为一种植物毒素和广谱抗菌化合物。除了其杀线虫特性外，我们在此表明玉米赤霉烯酮还能杀死酿酒酵母和粟酒裂殖酵母。我们还对zmn基因簇的表达及玉米赤霉烯酮产生的调控进行了研究。该基因簇的转录具有生长阶段依赖性，并受转录后RNA伴侣Hfq的调节。本研究结果表明，玉米赤霉烯酮是一种毒性很强的分子，在非常多样的生物系统中几乎没有明显的宿主特异性。就目前情况而言，玉米赤霉烯酮可用作先导化合物，适用于化学修饰和构效分析。然而，由于在多种生物测定中存在广泛的非选择性毒性，未经修饰的玉米赤霉烯酮不太可能适合作为治疗用抗生素。
Soil bacteria can be prolific producers of secondary metabolites and other biologically active compounds of economic and clinical importance. These natural products are often synthesized by large multi-enzyme complexes such as polyketide synthases (PKSs) or non-ribosomal peptide synthases (NRPSs). The plant-associated Gram-negative bacterium, Serratia plymuthica A153, produces several secondary metabolites and is capable of killing the nematode worm Caenorhabditis elegans; a commonly used model for the study of bacterial virulence. In this study, we show that disruption of the hybrid PKS/NRPS zeamine (zmn) gene cluster results in the attenuation of “fast-killing” of C. elegans, indicating that zeamine has nematicidal activity. C. elegans also exhibits age-dependent susceptibility to zeamine, with younger worms being most sensitive to the bioactive molecule. The zmn gene cluster is widely distributed within Serratia and phytopathogenic Dickeya species and investigation of strains harboring the zmn gene cluster showed that several of them are highly virulent in C. elegans. Zeamine was described previously as a phytotoxin and broad-spectrum antibacterial compound. In addition to its nematicidal properties, we show here that zeamine can also kill Saccharomyces cerevisiae and Schizosaccharomyces pombe. The expression of the zmn gene cluster and regulation of zeamine production were also investigated. Transcription of the cluster was growth phase-dependent, and was modulated by the post-transcriptional RNA chaperone, Hfq. The results of this study show that zeamine is a highly toxic molecule with little, or no, apparent host specificity in very diverse biological systems. In its current form, zeamine(s) may be useful as a lead compound suitable for chemical modification and structure-activity assays. However, because of widespread non-selective toxicity in multiple bioassays, unmodified zeamine(s) is unlikely to be suitable as a therapeutic antibiotic.
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影响因子：
3.1
作者：
Couillault, C;Ewbank, JJ
通讯作者：
Ewbank, JJ
DOI：
10.1073/pnas.1934677100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Challis, GL;Hopwood, DA
通讯作者：
Hopwood, DA
影响因子：
3.6
作者：
Fuernkranz, Michael;Lukesch, Birgit;Berg, Gabriele
通讯作者：
Berg, Gabriele
影响因子：
1.4
作者：
Gould, Marilyn;Nelson, Louise M.;Hynes, Russell K.
通讯作者：
Hynes, Russell K.
影响因子：
9.2
作者：
Aballay, A;Yorgey, P;Ausubel, FM
通讯作者：
Ausubel, FM