Superbugs in “Handcuffs”

By Sondra Forsyth

Staph infections become resistant to multiple antibiotics because of a genetic parasite called a plasmid that the bacteria carry. RepA is a protein that sticks to the beginning of the plasmid’s DNA sequence and starts a copying process. When a pair of RepA proteins bumps into another pair, which can happen when the cell is starting to get crowded with plasmids, the two pairs of RepA stick to each other and form a four-part molecule. Scientists say that the plasmids are therefore “handcuffed” because the plasmid can no longer replicate.

A team of researchers from Duke University and the University of Sydney in Australia has solved the structure of RepA. Knowing how this protein works may help researchers devise new ways to stop the plasmids from spreading antibiotic resistance in staph by preventing the plasmids from copying themselves. The study was published the week of June 9th 2014 in the Proceedings of the National Academy of Sciences.

A release from Duke quotes lead author Maria Schumacher as saying, “If plasmids can’t replicate, they go away. This is a fantastic new target for antibiotics . . . [RepA] is essential to everything. If you don’t have it, the plasmid will quickly cease to exist.”

Plasmids ferry genes from one kind of bacteria to another in a process called horizontal gene transfer. They also excel at adapting to environmental conditions more quickly than their bacterial hosts. Plasmids are able to develop new defenses to an antibiotic and then share that ability with other bacteria.

Schumacher says RepA is ubiquitous in the plasmid world and doesn’t bear much resemblance to other proteins, or to human protein. This fact makes it an attractive drug target.