NIH: Bacteriophage biology and engineering of E. coli phages

Antibiotic resistant bacteria are an increasing threat for the global human health. To find appropriate phages to use as a mean against antibiotic resistant bacteria, current methods are time consuming and inefficient. As most phages bind to their host recognizing specific receptors, a phages host range could be engineered by customizing their tail fibers. In this project we aim to predict binding between a phage and bacteria on genome sequences by developing a high quality, custom training data set, containing tail fiber amino acid sequences, host surface receptor sequences and quantitative binding values.

To accomplish this, first tail fibers and their complementary bacterial receptors must be identified by analyzing the putative tail fibers in silico and structurally. The kinetics of the tail fiber binding will be revealed by quantifying their binding efficiency with the help of GFP and bacterial receptors will be determined by testing infectivity on mutants. To find novel phage resistance mechanisms, bacterial strains are identified to which phages can bind without developing progeny. Here internal phage resistance mechanisms could be active. For the last task, phage binding during environmental conditions will be analyzed. 

The project is funded by National institute of Health NIH and involves collaboration with a number of international research labs including Professor Sam R. Nugen at Cornell University, US.

For more information please contact Professor Lone Brøndsted lobr@sund.ku.dk