The evolution of spectrum in antibiotics and bacteriocins.
The evolution of spectrum in antibiotics and bacteriocins.
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DOI：
10.1073/pnas.2205407119
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发表时间：
2022-09-20
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
抗生素，如青霉素，治疗各种感染。这种广谱的活性在微生物战争中有其进化根源，抗生素可以提供竞争优势。但细菌也会产生窄谱毒素，这就提出了一个难题：为什么不使用广谱毒素来瞄准更多的竞争对手呢？使用进化模型，我们表明，窄谱毒素有助于集中攻击一个关键的竞争对手，最大限度地减少毒素损失到其他目标。广谱攻击只有在微生物大量存在并能产生大量毒素时才有意义。我们调查了现有的数据，发现，正如预测的那样，广谱毒素通常是由高丰度的细菌产生的。这表明，抗生素是在优势微生物中进化出来的，这些微生物可以承受不同的竞争对手。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物种。这种广谱活动的进化根源在于生态竞争，细菌和其他微生物使用抗生素来抑制其他菌株和物种。然而，许多细菌也使用窄谱毒素，如细菌素，主要针对同种。为什么会有如此多样的频谱？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是最好的直觉，因为它使微生物能够杀死更广泛的竞争对手。然而，这个模型忽略了抗菌剂的一个重要特性：它们通常被它们所靶向的细胞结合、隔离或降解。减少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对手，避免在不太重要的物种上被耗尽。那么为什么广谱毒素会进化呢？我们的模型预测，如果一个菌株高度丰富，可以压倒它的主要竞争对手和其他物种，广谱毒素将受到自然选择的青睐。我们通过编译和分析用于细菌间竞争的毒素的调节和光谱的数据库来测试这一预测。该分析揭示了广谱毒素和密度依赖性调节之间的强烈关联，表明它们确实在菌株丰富时使用。我们的工作为为什么细菌通常会进化出细菌素等窄谱毒素提供了理论基础，并表明抗生素本身的进化是生态优势的标志。
Antibiotics, like penicillin, treat a wide range of infections. This broad-spectrum of activity has its evolutionary roots in microbial warfare, where antibiotics can provide a competitive edge. But bacteria also make narrow-spectrum toxins, which presents a puzzle: Why not use broad-spectrum toxins to target more competitors? Using evolutionary modelling, we show that narrow-spectrum toxins help focus an attack on a key competitor, minimizing toxin loss to other targets. Broad-spectrum attacks only make sense when a microbe is abundant and can make a lot of toxin. We survey available data and find, as predicted, that broad-spectrum toxins are typically made by bacteria at high abundance. This suggests that antibiotics evolved in dominant microbes that could afford to take on diverse competitors. 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.
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影响因子：
3.4
作者：
Procópio, Rudi Emerson de Lima;Silva, Ingrid Reis da;Araújo, Janete Magali de
通讯作者：
Araújo, Janete Magali de
影响因子：
2.8
作者：
Gordon, DM;Riley, MA
通讯作者：
Riley, MA
影响因子：
3.3
作者：
Feldgarden, M;Riley, MA
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Riley, MA
影响因子：
4.4
作者：
Chang W;Small DA;Toghrol F;Bentley WE
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Bentley WE
DOI：
10.1073/pnas.1608623113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Cochrane, Stephen A.;Findlay, Brandon;Vederas, John C.
通讯作者：
Vederas, John C.