Grant: Operating Grant

By studying how bacteria grow, and specifically how they choose to replicate their chromosomes, we can better understand how to control them with novel antibiotics that must be found to fight emerging resistant strains. Bacteria choose to replicate their chromosomes by starting at one place termed the replication origin, and they dedicate special proteins to act there to begin replicating. We isolated the replication origin and special proteins (called DnaA, CtrA and CC3319) from a common aquatic bacterium called Caulobacter crescentus. This bacterium is especially easy to study and therefore serves as a model for more difficult bacteria. Caulobacter's growth and chromosome replication can be followed in stages that display the steps required for chromosome replication. We eventually hope to understand how bacteria "decide" to replicate, and to a biochemist this means asking how proteins bind and influence each other during changing circumstances. When bacteria are tricked into making the wrong replicating decisions, they become much more vulnerable and less pathogenic. In the future, we might augment our dwindling arsenal of antibiotics if we find chemicals that bind special replication proteins and trick bacteria into making wrong (and often lethal) replication decisions.