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'Failed' experiment yields a biocontrol agent that doesn't trigger antibiotic resistance

MADISON - A failed experiment turned out to be anything but for bacteriologist Marcin Filutowicz.

As he was puzzling out why what should have been a routine procedure wouldn't work, he made a discovery that led to the creation of a new biological tool for destroying bacterial pathogens - one that doesn't appear to trigger antibiotic resistance.

The discovery also led to the startup of a promising new biotechnology firm that has already brought Wisconsin a dozen new, high-paying, highly skilled jobs. Filutowicz is a professor of bacteriology in the University of Wisconsin-Madison College of Agricultural and Life Sciences.

His inspiration came one morning in 1999 when he was puzzling over a failed experiment. A researcher in his lab had been trying to insert two different mutations into an ordinary bacterial plasmid - a routine task for the experienced scientist - but every attempt failed to produce a live bacterium.

Plasmids are circular DNA molecules that are different from chromosomal DNA, the genetic material that encodes the instructions for life in all cells. Plasmids are small, non-chromosomal DNA molecules. They are common in bacteria. The genes in plasmids often encode information that confers some selective advantage to their hosts - such as the ability to resist antibiotics.

Plasmids are useful tools for genetic engineering. It is relatively easy for a scientist to alter a plasmid's genetic makeup and then transfer the plasmid into a bacterium. The host bacterium then replicates the recombinant plasmid and transfers copies of it to other bacteria in a process called conjugation.

As he investigated the failed experiment, Filutowicz - who has spent two decades studying how plasmid replication is regulated - made a critical observation. A plasmid with one or the other of the benign mutations persisted, although it replicated a little more frequently than a mutation-free plasmid. How could it be, he wonder
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Source:University of Wisconsin-Madison


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