Marcin S. Filutowicz
Professor of Bacteriology
Plasmids are extra-chromosomal genetic elements that can be found in most bacteria. Remarkably, bacteria can exchange plasmids through several natural processes (transformation, transduction, and conjugation), sometimes sharing them with members of different genera. Our laboratory studies plasmids, using them to unravel the mechanisms that control DNA replication, maintenance, and partitioning. These processes are remarkably similar for plasmids and chromosomes (bacterial and eukaryotic), but plasmids offer an advantage to researchers; they can be evicted from cells whereas chromosomes cannot. This signature of all plasmids allows us to conveniently dissect, reassemble and introduce their DNA into various hosts, making them exemplary subjects for studying the basic properties of genetic material.
Different types of plasmids can be distinguished by the idiosyncrasies of plasmid-specific functional units called replicons, each of which has an origin of replication (ori) and related sequences. Researchers in our lab and others' have discovered a variety of plasmid- and host-encoded proteins that participate in plasmid replication and we are studying their recruitment to the ori and their roles in the replication process. Some of these proteins are regulators of replication that operate at or near the ori.
Many plasmids produce more than just the machinery they need for their own replication and transfer. They can also carry genes that confer a plethora of beneficial traits on their bacterial hosts, thereby indirectly enhancing their own (the plasmids') survival. Frequently, these genes are only useful intermittently or in certain environments. Examples include genes for antibiotic resistance, virulence, the degradation of unusual substrates and nitrogen fixation. Plasmid-borne antibiotic resistance is particularly problematic because plasmid transfer is allowing these genes to become ubiquitous in the environment. These important features have expanded our interests in plasmid biology beyond basic research. "Translational science" has its feet grounded in basic research while its eyes are on the prize of future applications. Recent efforts in our laboratory are focused on translating decades of knowledge about plasmid biology into new approaches to combat antibiotic-resistance and pathogenic bacteria. Specifically, we are working on disrupting the replication control of plasmids in ways that will attenuate or even kill their pathogenic bacterial hosts. Our various approaches to reprogramming the biology of plasmids may one day become useful applications in medical, veterinary and agricultural settings.