Svendsen Peter Bing, Henriksen Nathalie N S E, Jarmusch Scott A, Andersen Aaron J C, Smith Kirsty, Selsmark Marcus Weichel, Zhang Sheng-Da, Schostag Morten D, Gram Lone
Department of Biotechnology and Biomedicine, Center for Microbial Secondary Metabolites, Technical University of Denmark, Kgs. Lyngby, Denmark.
Department of Chemistry, University of Aberdeen, King's College, Aberdeen, United Kingdom.
Appl Environ Microbiol. 2024 Sep 18;90(9):e0058824. doi: 10.1128/aem.00588-24. Epub 2024 Aug 13.
Many bacteria co-exist and produce antibiotics, yet we know little about how they cope and occupy the same niche. The purpose of the present study was to determine if and how two potent antibiotic-producing marine bacteria influence the secondary metabolome of each other. We established an agar- and broth-based system allowing co-existence of a species and that, respectively, produce tropodithietic acid (TDA) and bromoalterochromides (BACs). Co-culturing of sp. strain A36a-5a on Marine Agar with strain B39bio caused a reduction of TDA production in the colony. We constructed a transcriptional gene reporter fusion in the gene in the TDA biosynthetic pathway in and demonstrated that the reduction of TDA by was due to the suppression of the TDA biosynthesis. A stable liquid co-cultivation system was developed, and the expression of in was reduced eightfold lower (per cell) in the co-culture compared to the monoculture. Mass spectrometry imaging of co-cultured colonies revealed a reduction of TDA and indicated that BACs diffused into the colony. BACs were purified from ; however, when added as pure compounds or a mixture they did not influence TDA production. In co-culture, the metabolome was dominated by features indicating that production of other compounds besides TDA was reduced. In conclusion, co-existence of two antibiotic-producing bacteria may be allowed by one causing reduction in the antagonistic potential of the other. The reduction (here of TDA) was not caused by degradation but by a yet uncharacterized mechanism allowing to reduce expression of the TDA biosynthetic pathway.IMPORTANCEThe drug potential of antimicrobial secondary metabolites has been the main driver of research into these compounds. However, in recent years, their natural role in microbial systems and microbiomes has become important to determine the assembly and development of microbiomes. Herein, we demonstrate that two potent antibiotic-producing bacteria can co-exist, and one mechanism allowing the co-existence is the specific reduction of antibiotic production in one bacterium by the other. Understanding the molecular mechanisms in complex interactions provides insights for applied uses, such as when developing TDA-producing bacteria for use as biocontrol in aquaculture.
许多细菌共存并产生抗生素，但我们对它们如何在同一生态位中生存和占据知之甚少。本研究的目的是确定两种强效产抗生素海洋细菌是否以及如何相互影响次级代谢组。我们建立了一个基于琼脂和肉汤的系统，使分别产生 tropodithietic 酸（TDA）和溴化变色菌素（BACs）的两种细菌能够共存。在海洋琼脂上，将 sp. 菌株 A36a - 5a 与 菌株 B39bio 共培养导致 菌落中 TDA 产量降低。我们在 的 TDA 生物合成途径中的 基因中构建了转录基因报告融合体，并证明 导致的 TDA 减少是由于 TDA 生物合成受到抑制。开发了一种稳定的液体共培养系统，与单培养相比，共培养中 中 的表达（每个细胞）降低了八倍。对共培养菌落的质谱成像显示 TDA 减少，并表明 BACs 扩散到了 菌落中。BACs 是从 中纯化出来的；然而，当作为纯化合物或混合物添加时，它们并不影响 TDA 的产生。在共培养中，代谢组以 特征为主，这表明除了 TDA 之外，其他 化合物的产生也减少了。总之，可以允许两种产抗生素细菌共存，一种细菌可导致另一种细菌的拮抗潜力降低。这种降低（此处指 TDA 的降低）不是由降解引起的，而是由一种尚未明确的机制导致的，该机制使 能够降低 TDA 生物合成途径的表达。重要性抗菌次级代谢产物的药物潜力一直是对这些化合物进行研究的主要驱动力。然而，近年来，它们在微生物系统和微生物群落中的天然作用对于确定微生物群落的组装和发育变得至关重要。在此，我们证明了两种强效产抗生素细菌可以共存，一种允许共存 的机制是一种细菌特异性降低另一种细菌的抗生素产量。了解复杂相互作用中的分子机制为实际应用提供了见解，例如在开发用于水产养殖生物防治的产 TDA 细菌时。
