MOLECULAR EVOLUTION OF ENTERIC BACTERIOCINS

微生物正在进行一场永无止境的军备竞赛。 这种微生物战在很大程度上是针对同种和近亲，它们与它们竞争最激烈的生态位和营养资源。 这种激烈竞争的一个进化结果是大多数细菌产生的抗菌化合物的多样性。 令人惊讶的是，很少有人关注这些化合物在天然微生物群落中的作用或它们的进化。 一类抗微生物剂，细菌素，已经受到越来越多的关注，因为观察到令人惊讶的高水平的细菌素多样性，细菌素在细菌中的广泛分布，以及细菌素在食品工业中作为防腐剂和在人类健康工业中作为抗生素的用途。 我们现在对细菌素介导的杀伤、细胞识别和转运到细胞中所涉及的分子机制有了深入的了解。 然而，很少有人致力于解决生态和进化问题，例如：这些毒素在介导微生物相互作用中发挥什么作用，这类异质蛋白质的起源和进化关系是什么，它们的多样化涉及哪些分子机制，以及对这些武器库的进化反应是什么，即防御机制和由此产生的进化军备竞赛？ 本研究提案的重点是具体解决这些问题。我们建议提供一个详细的描述的频率和分布的细菌素生产和耐药性的一个临床相关的，部门的细菌，肠杆菌科。 新的细菌素将被克隆和测序。 这些数据将帮助我们确定细菌素作用的系统发育范围，自然发生的抗性水平，以及确定肠道细菌素之间的进化关系及其多样化模式。 从本质上讲，我们的建议是探索细菌素的自然历史，以更好地了解细菌素和其他相关的抗菌剂如何用于替代或补充经典抗生素。 我们对细菌素的自然作用的理解，以及细菌群落中对细菌素的防御，可以直接应用于合理应用新型抗菌剂来解决人类健康问题

Microbes are engaged in a never-ending arms race. This microbial warfare is directed in large part at conspecifics and close relatives with which they compete most intensively for access to niches and nutritional resources. One evolutionary consequence of this intense competition is the diversity of antimicrobial compounds that most species of bacteria produce. Surprisingly, there has been little attention paid to understanding either the role these compounds play in natural microbial communities or their evolution. One class of antimicrobials, the bacteriocins, has received increasing attention because of the surprisingly high levels of bacteriocin diversity observed, the widespread distribution of bacteriocins in bacteria, and the use of bacteriocins as preservatives in the food industry and as antibiotics in the human health industry. We now have a sophisticated understanding of the molecular mechanisms involved in bacteriocin-mediated killing, cell recognition and transport into the cell. However, very little effort has been focused on addressing ecological and evolutionary questions, such as: what role do these toxins play in mediating microbial interactions, what are the origins of and evolutionary relationships among this heterogeneous class of proteins, what molecular mechanisms are involved in their diversification, and what are the evolutionary responses to such an arsenal of weapons, i.e. the mechanisms of defense and the resulting evolutionary arms race? The focus of this research proposal is to specifically tackle these issues. We propose to provide a detailed description of the frequency and distribution of bacteriocin production and resistance in one clinically relevant, division of bacteria, the Enterobacteriaceae. Novel bacteriocins will then be cloned and sequenced. These data will help us to determine the phylogenetic range over which bacteriocins act, the levels of naturally occurring resistance, as well as determine the evolutionary relationships among enteric bacteriocins and their modes of diversification. In essence, what we propose is to explore the natural history of bacteriocins in search of a better understanding of how bacteriocins, and other related antimicrobials, can be used to replace, or supplement, classical antibiotics. The understanding that we gain regarding the natural role of bacteriocins, and the defenses raised against them within bacterial communities, can be directly applied to the rational application of novels antimicrobials to human health issues