Hebrew U Research May Lead to Antibiotics of the Future
New research at Hebrew University, in conjunction with the University of Vienna, could help scientists create a new generation of novel, powerful antibiotics to overcome serious public health problems, replacing antibiotics that in recent years have become less effective, as generations of bacteria have developed resistance to them.
The research, led by Professor Hanna Engelberg-Kulka of the Institute for Medical Research Israel Canada (IMRIC) at the Hebrew University–Hadassah Medical School and her students, along with Professor Isabella Moll of the University of Vienna, shows for the first time how a stress-induced machinery of protein synthesis can destroy bacteria cells. The research greatly enhances the understanding by researchers of protein synthesis under stress conditions affect bacteria.
Over the past 50 years, the biological machinery responsible for protein synthesis has been extensively studied, in particular in the Escherichia coli (E. coli) bacteria, a gastric bacteria responsible for anything from stomach aches to food poisoning. The machinery of protein synthesis operates primarily through ribosomes -- small particle present in large numbers in every living cell whose function is to convert genetic information into protein molecules -- and messenger RNAs (mRNAs), which transfer the genetic information from the genome to the ribosomes and thereby direct the creation or synthesis of cell proteins.
In an article in a recent issue of the journal Cell, Professor Engelberg-Kulka and the other members of the research team described the discovery of a novel molecular machinery for protein synthesis that is generated and operates under stress conditions in E. coli. The study described in the article shows, for the first time, how under stress conditions, such as nutrient starvation and antibiotics, the synthesis of a specific toxic protein is induced that causes a change in the protein-synthesizing machinery of the bacteria. This toxic protein cleaves parts of the ribosome and the mRNAs, thereby preventing the usual interaction between these two components.
As a result, an alternative protein-synthesizing machinery is generates. It includes a specialized sub-class of ribosomes, called "stress ribosomes," which is involved in the selective synthesis of proteins that are directed by the sliced mRNAs, and is responsible for bacterial cell death. In other words, the toxic protein disrupts the normal behavior of the E. coli cells, leading to their deaths – thus ridding the body of the bacteria. The discovery of a "stress-induced protein synthesizing machinery" may offer a new way for the design of improved, novel antibiotics that could effectively utilize the stress-inducing mechanism process in order to more efficiently cripple pathogenic bacteria. Research on the project will continue, and Professor Engelberg-Kulka believes that further work in this area “should contribute to our understanding of that fundamental biological phenomenon, the multi-cellular behavior of bacterial cultures.”