Studies of Iron-Pumping Bacteria May Lead to New Antibiotics

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The war against drug-resistant bacteria continues to intensify. A few years ago, hospital workers detected strains of Staphylococcus aureus--the primary cause of hospital-acquired infections--that are resistant to every known antibiotic medicine. Major killers worldwide such as pneumonia, malaria, tuberculosis, cholera, and gonorrhea are progressively defying all treatment options. And with the ease of international travel, a drug-resistant microbe originating oversees can arrive on U.S. shores within 24 hours. To stem the rising tide of drug-resistant bacteria, scientists are scrambling to design new drugs.

To become and remain infectious, many disease-causing bacteria literally "pump iron." That is, they pump the metal from their hosts' bodies into their cells using proteins in their outer membranes that open and close. These transporter proteins are found in dangerous bacteria such as those that cause cholera, dysentery, blood poisoning, meningitis, and plague.

This year, Dr. Dick van der Helm of the University of Oklahoma, Norman, revealed the structural details of one iron-pumping transporter protein called FecA. According to the new three-dimensional image, FecA looks like a barrel that is open on both ends and plugged in the middle. After iron (and a special carrier protein) enters from the top, this entrance closes behind it, the FecA plug opens, and the iron passes through into the bacterial cell.

A better understanding of how disease-causing bacteria become infectious may lead to new drugs to treat such diseases. Scientists may be able to design novel antibiotics that physically mimic the natural iron carriers. The idea is that the transporter proteins would latch onto the drugs, "think" they contain iron, and actively pump them into bacteria. Once inside, instead of arming the bacteria for infection, the drugs would kill the bacteria. Now that scientists know how the transporter proteins operate, they can try various ways to manipulate them to admit drugs or to keep out iron. More generally, the study improves our understanding of how bacteria obtain essential nutrients.