Vieira Ana R, Camacho Francisco, Sousa Maria L, Luelmo Sara, Santarém Nuno, Cordeiro-da-Silva Anabela, Leão Pedro N
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Matosinhos, Portugal.
Department of Biology and Chemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
Microb Ecol. 2025 Mar 4;88(1):9. doi: 10.1007/s00248-025-02507-2.
Cyanobacteria, known to be rich sources of valuable natural products (NPs) with relevant biological properties, are a unique subject to study the interplay between chemistry and ecology. Cultivation of cyanobacteria as isolated strains may only reveal a small fraction of their NPs. In contrast, investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Cyanobacteria and amoebae are known to co-exist in diverse environments, but the interaction between these organisms has been poorly investigated. Defense strategies against grazer organisms may rely on morphological changes including biofilm formation or increased motility; however, secretion of toxic metabolites seems to be more effective on this regard. Among the most structurally unique cyanobacterial secondary metabolites is nocuolin A, an 1,2,3-oxadiazine metabolite isolated from the cyanobacterial strain Nodularia sp. LEGE 06071 that exhibits potent anti-proliferative activity against several human cancer lines, associated with impairment of mitochondrial oxidative phosphorylation. In this work, we show that nocuolin A is toxic against two well-known model amoebae, Acanthamoeba and Dictyostelium, leading to amoebae encystation and decrease in viability. In addition, in lawn grazing assays, we observed that Nodularia sp. LEGE 06071, the producer strain of nocuolin A, was not grazed by amoeba, while a related strain, which does not produce detectable levels of nocuolin A, was. These results support the possible involvement of nocuolin A as a chemical mediator during the interaction between these organisms. Furthermore, we show that this cyanobacterial metabolite also exhibits potent toxicity against other protozoan organisms and a free-living nematode, making it an interesting broad-spectrum scaffold for the development of antiprotozoal or anti-helminthic drugs.
蓝藻细菌是已知富含具有相关生物学特性的珍贵天然产物（NPs）的来源，是研究化学与生态相互作用的独特对象。将蓝藻细菌作为分离菌株进行培养可能只能揭示其NPs的一小部分。相比之下，从生态学角度研究微生物相互作用是揭示新化学物质和生物活性的特别富有成效的方法。已知蓝藻细菌和变形虫在多种环境中共存，但这些生物体之间的相互作用研究较少。针对食草生物的防御策略可能依赖于形态变化，包括生物膜形成或运动性增加；然而，有毒代谢物的分泌在这方面似乎更有效。在结构最独特的蓝藻细菌次级代谢产物中，有诺库林A，一种从蓝藻细菌结节藻属菌株LEGE 06071中分离出的1,2,3-恶二嗪代谢物，它对几种人类癌细胞系表现出强大的抗增殖活性，与线粒体氧化磷酸化受损有关。在这项工作中，我们表明诺库林A对两种著名的模型变形虫，棘阿米巴和盘基网柄菌有毒性，导致变形虫形成包囊并降低活力。此外，在草坪啃食试验中，我们观察到诺库林A的产生菌株结节藻属LEGE 06071未被变形虫啃食，而一种不产生可检测水平诺库林A的相关菌株则被啃食。这些结果支持诺库林A可能作为这些生物体之间相互作用的化学介质。此外，我们表明这种蓝藻细菌代谢物对其他原生动物和一种自由生活的线虫也表现出强大的毒性，使其成为开发抗原生动物或抗蠕虫药物的有趣的广谱支架。
