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.
