How a phage-derived weapon system shapes interbacterial interactions within and across species

细菌产生许多不同的产品，以便在自然界中与其他生物竞争。这些产品中的一个子集成功地开发成了与医学相关的抗生素。然而，这些抗生素中的许多针对的是广泛类别的细菌。因此，它们用于治疗有害感染也可能是有害的，因为它们消除了有益的细菌。因此，寻找和开发新的抗生素，准确地针对感兴趣的细菌菌株，避免有害的偏离目标的影响，是至关重要的。Baltrus实验室发现并鉴定了一类由植物病原菌紫丁香假单胞菌产生的潜在抗生素(紫丁香素)。尾毛虫似乎非常强大。人们认为，只要一个分子就足以杀死接触到的细菌。Tailocins对杀灭细菌菌株也具有高度的特异性。该奖项的目标是确定taroocin如何与其他细菌结合并杀死其他细菌，以及细菌如何对traocin产生抗药性。这些信息可以用来设计一类新的抗生素。该奖项的另一个目标是确定另一种细菌(Pantoea)通过新途径的基因特征来产生类似分子的潜力。还将开发一种开放获取的计算管道，可用于筛选细菌基因组序列中额外的TRACIN类分子。本科生还将有机会在实验室工作，为培养下一代科学家提供平台。细菌素由细菌细胞产生，被认为专门针对并杀死同一物种的不同菌株，或密切相关的细菌物种。细菌素的这种相对特异的杀灭光谱可以提供一种强有力的手段来精确操纵微生物群，同时避免与广谱抗生素相关的脱靶效应。Baltrus实验室最近鉴定了一类由植物病原菌紫丁香假单胞菌产生的噬菌体衍生细菌素(R型丁香素或尾菌素)。与教条相反，尾菌素可以杀死紫丁香假单胞菌自然遇到的各种不同的细菌种类。这项资助的目标是确定这一更广泛活动的遗传基础，并确定taroocin敏感性的分子基础。这些信息将使科学家能够更好地预测细菌素在不同菌株之间的杀灭结果。该奖项将开发可自由访问的计算工具，从而能够在不同的细菌分类群中发现新的噬菌体衍生细菌素。总体而言，这项研究将提高以极高的精度操纵微生物群落的能力，并将使发现新的类似TRAN的系统被开发和挖掘，用于未来的相互作用。此外，本科生将有机会在实验室工作，提供一个教授下一代科学家的平台。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Bacteria produce many different products to outcompete other organisms in nature. One subset of these products was developed successfully into medically relevant antibiotics. However, many of these antibiotics target broad classes of bacteria. Thus, their use to treat harmful infections may also be detrimental because they eliminate beneficial bacteria. It is therefore critical to find and develop new antibiotics that precisely target bacterial strains of interest and avoid detrimental off-target effects. The Baltrus lab discovered and characterized a class of potential antibiotics (tailocins) produced by the plant pathogen Pseudomonas syringae. Tailocins appear to be very powerful. It is thought that just one molecule is sufficient to kill a bacterium on contact. Tailocins also are highly specific for killing of bacterial strains. The goal of this award is to identify how tailocins bind to and kill other bacteria, and how bacteria can develop resistance to tailocin. This information can be used to engineer a new class of antibiotics. An additional goal of this award is to identify the potential for another bacterium (Pantoea) to produce similar molecules through genetic characterization of new pathways. There also will be the development of an open access computational pipeline that can be used to screen bacterial genome sequences for additional tailocin-like molecules. Undergraduate students will also have the opportunity to work in the laboratory, providing a platform to develop the next generation of scientists. Bacteriocins produced by bacterial cells, and are thought to specifically target and kill different strains of the same species, or closely related bacterial species. This relatively specific killing spectrum of bacteriocins could provide a powerful means to precisely manipulate microbiomes while avoiding off-target effects associated with broad spectrum antibiotics. The Baltrus lab recently characterized a class of phage-derived bacteriocins (R-type syringacins or tailocins) produced by the plant pathogen Pseudomonas syringae. Contrary to dogma, tailocins can kill a variety of different bacterial species naturally encountered by P. syringae. Goals of this grant are to pinpoint the genetic basis for this broader activity, and to identify the molecular basis of tailocin sensitivity. This information will allow scientists to better predict the outcomes of bacteriocin killing across strains. This award will develop freely-accessible computational tools that will enable discovery of new phage-derived bacteriocins across diverse bacterial taxa. Overall, this research will increase the ability to manipulate microbial communities with great precision, and will enable the discovery of new tailocin-like systems to be developed and mined for interactions in the future. In addition, undergraduate students will have the opportunity to work in the laboratory, providing a platform to teach the next generation of scientists.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.