The development of antibiotic multiresistant bacteria has become a serious problem for modern medicine in the treatment of bacterial infectious diseases. The urgent need for new antimicrobial compounds is in contrast to the dwindling number of new antimicrobial agents entering the market. In order to develop new antibiotics it is desirable to identify previously unknown target sites for antimicrobial action. Gene products that are essential for cell viability are the present preferred targets.
This project is set up to develop a novel system based upon transposon insertion mutagenesis to be able to control protein levels in living cells. This system will allow the generation of a library of insertion mutants in the chromosomes of a number of different pathogenic bacteria. In each clone it will enable the inducible rapid knock-down of protein levels from a tagged gene. In the case of essential genes this will both identify the complement of essential genes in an organism and allow the study of the phenotype of knocking out an essential protein in real time. The ultimate goal will be to generate representative libraries of insertions in three important bacterial pathogens: Escherichia coli, Staphylococcus aureus and Acinetobacter sp.