Abrudan Monica I, Smakman Fokko, Grimbergen Ard Jan, Westhoff Sanne, Miller Eric L, van Wezel Gilles P, Rozen Daniel E
Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, United Kingdom;
Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands;
Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11054-9. doi: 10.1073/pnas.1504076112. Epub 2015 Jul 27.
Despite their importance for humans, there is little consensus on the function of antibiotics in nature for the bacteria that produce them. Classical explanations suggest that bacteria use antibiotics as weapons to kill or inhibit competitors, whereas a recent alternative hypothesis states that antibiotics are signals that coordinate cooperative social interactions between coexisting bacteria. Here we distinguish these hypotheses in the prolific antibiotic-producing genus Streptomyces and provide strong evidence that antibiotics are weapons whose expression is significantly influenced by social and competitive interactions between competing strains. We show that cells induce facultative responses to cues produced by competitors by (i) increasing their own antibiotic production, thereby decreasing costs associated with constitutive synthesis of these expensive products, and (ii) by suppressing antibiotic production in competitors, thereby reducing direct threats to themselves. These results thus show that although antibiotic production is profoundly social, it is emphatically not cooperative. Using computer simulations, we next show that these facultative strategies can facilitate the maintenance of biodiversity in a community context by converting lethal interactions between neighboring colonies to neutral interactions where neither strain excludes the other. Thus, just as bacteriocins can lead to increased diversity via rock-paper-scissors dynamics, so too can antibiotics via elicitation and suppression. Our results reveal that social interactions are crucial for understanding antibiosis and bacterial community dynamics, and highlight the potential of interbacterial interactions for novel drug discovery by eliciting pathways that mediate interference competition.
尽管抗生素对人类至关重要,但对于产生抗生素的细菌而言,其在自然界中的功能却几乎没有达成共识。传统解释认为,细菌将抗生素用作杀死或抑制竞争对手的武器,而最近的一种替代假说则指出,抗生素是协调共存细菌之间合作性社会互动的信号。在这里,我们在 prolific antibiotic-producing genus Streptomyces 中区分了这些假说,并提供了有力证据,证明抗生素是武器,其表达受到竞争菌株之间社会和竞争相互作用的显著影响。我们表明,细胞通过以下方式对竞争对手产生的信号做出兼性反应:(i)增加自身抗生素的产量,从而降低与这些昂贵产品的组成型合成相关的成本;(ii)抑制竞争对手的抗生素生产,从而减少对自身的直接威胁。因此,这些结果表明,尽管抗生素的产生具有深刻的社会性,但绝不是合作性的。接下来,我们通过计算机模拟表明,这些兼性策略可以通过将相邻菌落之间的致命相互作用转化为中性相互作用(即两种菌株都不排斥对方),从而促进群落环境中生物多样性的维持。因此,就像细菌素可以通过剪刀石头布动态导致多样性增加一样,抗生素也可以通过诱导和抑制来实现。我们的结果表明,社会相互作用对于理解抗菌作用和细菌群落动态至关重要,并强调了细菌间相互作用通过引发介导干扰竞争的途径在新型药物发现方面的潜力。