原文链接：Antagonism correlates with metabolic similarity in diverse bacteria | PNAS

Significance

Diverse species from all over the bacterial tree of life produce antibiotics to limit the growth of competitors and thereby enhance their resource availability. Here we examined the pairwise inhibition between bacterial species from natural settings. We find that bacteria mainly inhibit the growth of metabolically similar and evolutionary related species, in line with Darwin’s age old competition-relatedness hypothesis. We further find that inhibiting the growth of other species is associated with a generalist lifestyle, suggesting a trade-off between specialists efficiently growing on few resources and generalists who are able to use many resources but have to inhibit the specialists to obtain them.

重要意义

细菌生命树上的各种物种都会产生抗生素，以限制竞争对手的生长，从而提高自身的资源可用性。在这里，我们研究了自然环境中细菌物种之间的配对抑制作用。我们发现，细菌主要抑制代谢相似、进化相关的物种的生长，这与达尔文古老的竞争相关性假说一致。我们还发现，抑制其他物种的生长与通才的生活方式有关，这表明在利用少量资源高效生长的专才与能够利用大量资源但必须抑制专才才能获得这些资源的通才之间存在一种权衡。

Abstract

In the Origin of Species, Charles R. Darwin [Darwin C (1859) On the Origin of Species] proposed that the struggle for existence must be most intense among closely related species by means of their functional similarity. It has been hypothesized that this similarity, which results in resource competition, is the driver of the evolution of antagonism among bacteria. Consequently, antagonism should mostly be prevalent among phylogenetically and metabolically similar species. We tested the hypothesis by screening for antagonism among all possible pairwise interactions between 67 bacterial species from 8 different environments: 2,211 pairs of species and 4,422 interactions. We found a clear association between antagonism and phylogenetic distance, antagonism being most likely among closely related species. We determined two metabolic distances between our strains: one by scoring their growth on various natural carbon sources and the other by creating metabolic networks of predicted genomes. For both metabolic distances, we found that the probability of antagonism increased the more metabolically similar the strains were. Moreover, our results were not compounded by whether the antagonism was between sympatric or allopatric strains. Intriguingly, for each interaction the antagonizing strain was more likely to have a wider metabolic niche than the antagonized strain: that is, larger metabolic networks and growth on more carbon sources. This indicates an association between an antagonistic and a generalist strategy.

摘要

在《物种起源》中，查尔斯·R·达尔文（Darwin C (1859) On the Origin of Species）提出，由于功能相似性，近亲物种之间的生存竞争必定最为激烈。有人假设，这种相似性导致了资源竞争，是细菌对抗性进化的驱动力。因此，对抗性应该主要存在于系统发育和代谢相似的物种中。我们通过筛选来自 8 个不同环境的 67 种细菌物种之间所有可能的成对相互作用中的对抗性来检验这一假设：2,211 对物种和 4,422 种相互作用。我们发现对抗性与系统发育距离之间存在明显的关联，近亲物种之间最有可能存在对抗性。我们确定了菌株之间的两种代谢距离：一种是通过对它们在各种天然碳源上的生长进行评分，另一种是通过创建预测基因组的代谢网络。对于这两种代谢距离，我们发现菌株的代谢越相似，对抗的可能性就越大。此外，我们的结果并没有因拮抗作用是同域菌株还是异域菌株之间而发生变化。有趣的是，对于每次相互作用，拮抗菌株更有可能比被拮抗菌株具有更宽的代谢生态位：即更大的代谢网络和在更多碳源上生长。这表明拮抗策略与通才策略之间存在关联。

图1 (A) 细菌主要拮抗密切相关的基因型； 抑制概率随 16S rRNA 基因系统发育距离的减小而增加。红线为逻辑回归，灰色阴影区域表示 95% 的置信区间(P < 0.001，n = 2 211）。(B) 少数菌株抑制其他许多菌株，但这些超级杀手在系统发育中随机分布。

图3 (A) 当观察到拮抗作用时，拮抗剂与被拮抗剂的代谢网络大小之比大于 1（P = 0），但在其余相互作用中与 1 无差异（P = 0.99）。(B) 当观察到拮抗作用时，拮抗剂生长的碳源数量与被拮抗剂生长的碳源数量之间的 log2 比值大于 0 (P = 0.03)，但其余相互作用的 log2 比值与 0 无差异 (P = 1)。P 值是对中位数是否大于 1（A）或 0（B）的单尾检验，由 1,000 次引导实测估算得出。点为中位数，误差条为中位数的 90% 自举置信区间（相当于中位数的 5% 单尾检验）。(拮抗 “和 ”无拮抗 "分别为 n = 148 和 n = 4,274）。

图2 (A) 通过重叠代谢网络中的化合物（节点），计算出所有菌株对之间的功能距离。(B）抑制概率随功能距离的减小而增加。红线为逻辑回归，灰色阴影区域表示 95% 的置信区间（P < 0.001，n = 2,211）。(C) 根据它们在 BiOLOG 生态板上的生长模式计算出的抑制概率随代谢距离的减少而增加。红线为逻辑回归，灰色阴影区域表示 95% 的置信区间（P = 0.0023，n = 1,770）。

图4 (A）无论是同域菌株还是异域菌株，抑制性相互作用的比例没有差异（OR = 0.97，P = 0.90，费雪精确检验）。(B和C）系统发育或功能距离的分布在同域和异域菌株之间没有差异，但代谢相似（D）的同域菌株比例过高。

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