Iowa State, Ames Lab researchers identify structure that allows bacteria to resist drugs

A research team led by Edward Yu of Iowa State University and the Ames Laboratory has discovered the crystal structures of pumps that remove heavy metal toxins from bacteria, making them resistant to antibiotics.

The findings are published in the Sept. 23 issue of the journal Nature.

Yu – an associate of the U.S. Department of Energy's Ames Laboratory and an Iowa State associate professor of chemistry, of physics and astronomy, of biochemistry, biophysics and molecular biology – said the finding gives researchers a better understanding of bacterial resistance to antibiotics. Ultimately it could help drug researchers develop treatments to combat that resistance.

To make their findings, the researchers purified and crystallized the membrane proteins that make up an efflux pump of E. coli bacteria. The researchers prepared some samples that contained the toxic heavy metals copper and silver and some that did not.

The researchers used X-ray crystallography to compare the various structures, identify the differences and understand the mechanism that removes heavy-metal toxins from cells.

Their paper specifically describes the crystal structure of CusA, one of three parts of the pumps responsible for removing toxins from bacteria. Yu said CusA is an inner membrane transporter which belongs to the resistance-nodulation-division protein superfamily. It consists of 1,047 amino acid residues and spans the inner membrane 12 times.