Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA.
mBio. 2020 May 19;11(3):e00948-20. doi: 10.1128/mBio.00948-20.
Antibiotics produced by bacteria play important roles in microbial interactions and competition Antibiosis can induce resistance mechanisms in target organisms, and at sublethal doses, antibiotics have been shown to globally alter gene expression patterns. Here, we show that hygromycin A from sp. strain 2AW. induces ATCC 31532 to produce the purple antibiotic violacein. Sublethal doses of other antibiotics that similarly target the polypeptide elongation step of translation likewise induced violacein production, unlike antibiotics with different targets. biofilm formation and virulence against were also induced by translation-inhibiting antibiotics, and we identified an ntibiotic-nduced esponse () two-component regulatory system that is required for these responses. Genetic analyses indicated a connection between the Air system, quorum-dependent signaling, and the negative regulator VioS, leading us to propose a model for induction of violacein production. This work suggests a novel mechanism of interspecies interaction in which a bacterium produces an antibiotic in response to inhibition by another bacterium and supports the role of antibiotics as signal molecules. Secondary metabolites play important roles in microbial communities, but their natural functions are often unknown and may be more complex than appreciated. While compounds with antibiotic activity are often assumed to underlie microbial competition, they may alternatively act as signal molecules. In either scenario, microorganisms might evolve responses to sublethal concentrations of these metabolites, either to protect themselves from inhibition or to change certain behaviors in response to the local abundance of another species. Here, we report that violacein production by ATCC 31532 is induced in response to hygromycin A from sp. 2AW, and we show that this response is dependent on inhibition of translational polypeptide elongation and a previously uncharacterized two-component regulatory system. The breadth of the transcriptional response beyond violacein induction suggests a surprisingly complex metabolite-mediated microbe-microbe interaction and supports the hypothesis that antibiotics evolved as signal molecules. These novel insights will inform predictive models of soil community dynamics and the unintended effects of clinical antibiotic administration.
细菌产生的抗生素在微生物相互作用和竞争中发挥着重要作用。抗生性可以诱导靶生物产生抗性机制，而且在亚致死剂量下，抗生素已被证明会全局改变基因表达模式。在这里，我们展示了来自 sp. 2AW. 的 Hygromycin A 诱导 ATCC 31532 产生紫色抗生素紫霉素。其他类似靶向翻译延长步骤的抗生素的亚致死剂量同样诱导了紫霉素的产生，而与具有不同靶标的抗生素不同。翻译抑制抗生素也诱导了生物膜形成和对 的毒力，我们鉴定了一个抗生素诱导的反应（ARS）双组分调节系统，该系统是这些反应所必需的。遗传分析表明，Air 系统、群体感应信号和负调节因子 VioS 之间存在联系，这导致我们提出了一个紫霉素产生诱导模型。这项工作表明了一种新的种间相互作用机制，其中一种细菌会产生抗生素来响应另一种细菌的抑制作用，并支持抗生素作为信号分子的作用。次生代谢物在微生物群落中起着重要作用，但它们的自然功能通常未知，可能比预期的更为复杂。虽然具有抗生素活性的化合物通常被认为是微生物竞争的基础，但它们也可以作为信号分子。在这两种情况下，微生物可能会进化出对这些代谢物亚致死浓度的反应，要么是为了防止自身受到抑制，要么是为了响应另一种物种在当地的丰度变化而改变某些行为。在这里，我们报告说， ATCC 31532 产生的紫霉素是对来自 sp. 2AW 的 Hygromycin A 的响应，我们表明这种响应依赖于翻译多肽延伸的抑制和一个以前未被表征的双组分调节系统。紫霉素诱导之外的转录反应的广度表明了一种令人惊讶的复杂代谢物介导的微生物-微生物相互作用，并支持了抗生素作为信号分子进化的假说。这些新的见解将为土壤群落动态的预测模型和临床抗生素给药的意外影响提供信息。
