In the present study, adaptive laboratory evolution was used to stimulate antibiotic production in a weak antibiotic-producing Streptomyces strain JB140. The seven different competition experiments utilized three serial passages (three cycles of adaptation-selection of 15 days each) of a weak antibiotic-producing Streptomyces strain (wild-type) against one (biculture) or two (triculture) or three (quadriculture) target pathogens. This resulted in the evolution of a weak antibiotic-producing strain into the seven unique mutant phenotypes that acquired the ability to constitutively exhibit increased antimicrobial activity against bacterial pathogens. The mutant not only effectively inhibited the growth of the tested pathogens but also observed to produce antimicrobial against multidrug-resistant (MDR) E. coli. Intriguingly, the highest antimicrobial activity was registered with the Streptomyces mutants that were adaptively evolved against the three pathogens (quadriculture competition). In contrast to the adaptively evolved mutants, a weak antimicrobial activity was detected in the un-evolved, wild-type Streptomyces. To get molecular evidence of evolution, RAPD profiles of the wild-type Streptomyces and its evolved mutants were compared that revealed significant polymorphism among them. These results demonstrated that competition-based adaptive laboratory evolution method can constitute a platform for evolutionary engineering to select improved phenotypes (mutants) with increased production of antibiotics against targeted pathogens.

中文翻译：

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实验室适应性进化触发链霉菌中病原体依赖的广谱抗菌效力

在本研究中，适应性实验室进化被用来刺激抗生素产生能力较弱的链霉菌菌株JB140的抗生素产生。七个不同的竞争实验利用了产生抗生素的弱链霉菌菌株（野生型）针对一种（双培养）或两种（三培养）或三种（四次培养）靶标的三个连续传代（三个周期的适应性选择，每个周期为15天）。病原体。这导致弱的抗生素生产菌株进化为七个独特的突变表型，这些表型获得了组成性地表现出对细菌病原体增强的抗菌活性的能力。该突变体不仅有效地抑制了所测试病原体的生长，而且还观察到产生针对多重耐药性（MDR）大肠杆菌的抗菌剂。有趣的是 链霉菌突变体具有最高的抗菌活性，这些突变体针对三种病原体进行了适应性进化（四价菌竞争）。与适应性进化的突变体相反，在未进化的野生型链霉菌中检测到弱的抗菌活性。为了获得进化的分子证据，比较了野生型链霉菌及其进化突变体的RAPD图谱，发现它们之间存在明显的多态性。这些结果表明，基于竞争的适应性实验室进化方法可以构成进化工程的平台，以选择改良的表型（突变体），同时增加针对目标病原体的抗生素的产生。