A key property of many antibiotics is that they will kill or inhibit a diverse range of microbial species. This broad-spectrum of activity has its evolutionary roots in ecological competition, whereby bacteria and other microbes use antibiotics to suppress other strains and species. However, many bacteria also use narrow-spectrum toxins, such as bacteriocins, that principally target conspecifics. Why has such a diversity in spectrum evolved? Here, we develop an evolutionary model to understand antimicrobial spectrum. Our first model recapitulates the intuition that broad-spectrum is best, because it enables a microbe to kill a wider diversity of competitors. However, this model neglects an important property of antimicrobials: They are commonly bound, sequestered, or degraded by the cells they target. Incorporating this toxin loss reveals a major advantage to narrow-spectrum toxins: They target the strongest ecological competitor and avoid being used up on less important species. Why then would broad-spectrum toxins ever evolve? Our model predicts that broad-spectrum toxins will be favored by natural selection if a strain is highly abundant and can overpower both its key competitor and other species. We test this prediction by compiling and analyzing a database of the regulation and spectrum of toxins used in inter-bacterial competition. This analysis reveals a strong association between broad-spectrum toxins and density-dependent regulation, indicating that they are indeed used when strains are abundant. Our work provides a rationale for why bacteria commonly evolve narrow-spectrum toxins such as bacteriocins and suggests that the evolution of antibiotics proper is a signature of ecological dominance.

中文翻译：

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抗生素和细菌素的光谱演变

许多抗生素的一个关键特性是它们会杀死或抑制多种微生物。这种广谱活动的进化根源在于生态竞争，细菌和其他微生物利用抗生素来抑制其他菌株和物种。然而，许多细菌也使用主要针对同种生物的窄谱毒素，例如细菌素。为什么会进化出如此多样化的频谱？在这里，我们开发了一个进化模型来了解抗菌谱。我们的第一个模型概括了广谱最好的直觉，因为它使微生物能够杀死更广泛的竞争者。然而，该模型忽略了抗菌剂的一个重要特性：它们通常被它们所针对的细胞结合、隔离或降解。结合这种毒素损失揭示了窄谱毒素的一个主要优势：它们针对最强的生态竞争者，避免被不那么重要的物种耗尽。那么为什么会进化出广谱毒素呢？我们的模型预测，如果一种菌株非常丰富并且可以压倒其主要竞争对手和其他物种，那么广谱毒素将受到自然选择的青睐。我们通过编译和分析细菌间竞争中使用的毒素的调节和光谱数据库来测试这一预测。该分析揭示了广谱毒素与密度依赖性调节之间的密切关联，表明它们确实在菌株丰富时使用。