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

细菌产生许多不同的产品，以胜过自然界中的其他生物。这些产品的一个子集已成功开发成医学相关的抗生素。然而，这些抗生素中的许多针对广泛的细菌类别。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细菌。 因此，寻找和开发精确靶向感兴趣的细菌菌株并避免有害的脱靶效应的新抗生素至关重要。Baltrus实验室发现并表征了一类由植物病原体假单胞菌产生的潜在抗生素（tailocins）。Tailocins似乎非常强大。人们认为，只要一个分子就足以杀死接触的细菌。 Tailocins也对杀死细菌菌株具有高度特异性。该奖项的目标是确定tailocin如何结合并杀死其他细菌，以及细菌如何对tailocin产生耐药性。这些信息可以用来设计一种新的抗生素。该奖项的另一个目标是确定另一种细菌（泛菌属）通过新途径的遗传表征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的其他尾蛋白样分子。本科生也将有机会在实验室工作，为培养下一代科学家提供平台。 由细菌细胞产生的细菌素，被认为特异性靶向并杀死同一物种或密切相关的细菌物种的不同菌株。细菌素的这种相对特异性的杀伤谱可以提供一种强有力的手段来精确操纵微生物组，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体假单胞菌产生的噬菌体衍生的细菌素（R型细菌素或尾孢菌素）。与教条相反，tailocins可以杀死由P.lingae自然遇到的各种不同的细菌物种。 这项资助的目标是查明这种更广泛活动的遗传基础，并确定tailocin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杀死菌株的结果。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。总的来说，这项研究将提高以非常精确的方式操纵微生物群落的能力，并将能够发现新的tailocin样系统，以便在未来开发和挖掘相互作用。此外，本科生将有机会在实验室工作，为下一代科学家提供教育平台。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值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.