Grant: Operating Grant

Chromosome segregation is a fundamental process for all organisms, from bacteria to man. All bacterial species contain small chromosomes called plasmids, which carry genes that benefit the bacterial host but are often harmful to human and animal health. For example, these plasmids are usually necessary for the pathogenicity and antibiotic resistance of bacteria. In addition, bacterial plasmids can transfer their genes to other bacteria, which contributes to the rapid spread of antibiotic resistance. The proper segregation of plasmids is necessary for their stable inheritance in bacterial cells. We study the segregation, or "partition", of a bacterial plasmid called P1 in Escherichia coli. P1 uses two plasmid encoded proteins, called ParA and ParB, to dynamically position plasmids inside cells during the bacterial cell cycle, which ensures that all cells will inherit a plasmid after cell division. My research involves the identification and characterization of all host- and plasmid encoded partition components, in order to define the mechanistic steps in, and to design methods to interfere with, this essential process. Genes for ParAs and ParBs have been identified in almost all bacterial species examined, and the list continues to grow as more microbial genomes are sequenced. The P1 plasmid is an excellent nonpathogenic model system for (a) maintenance of a variety of pathogenic bacterial and plasmid chromosomes and (b) the basic mechanisms of chromosome dynamics and segregation in all organisms. A better understanding of these maintenance mechanisms will lead to better ways to fight bacterial disease.