Researchers like Dr. Phillip Klebba, his colleagues at the University of Oklahoma, Norman, and Dr. Jimmy B. Feix at the Medical College of Wisconsin, Milwaukee, are working hard to provide the new approaches needed to combat the all-too-resilient organisms. In the May 23 issue of Science, Dr. Klebba and his group report that the membranes of many disease-causing bacteria admit iron (iron is necessary for the organisms to become pathogenic) through protein-gated pores that open and close. These pores are found in such highly dangerous bacteria as those that cause cholera, dysentery, blood poisoning, meningitis, and plague.
The Science paper shows that bacteria bind iron-containing molecules on the outside of a closed membrane protein, called FepA. After binding iron, the protein opens and then closes as it transports the metal into the cell. Now that the mechanisms by which the pores operate are known, researchers can proceed to study new approaches for fighting the pathogens, including ways to manipulate the gated pores to allow drugs to enter or to prevent iron from entering the cells.
The work also opens the field for further research on bacterial membrane transport mechanisms by showing that living cells can be studied without disrupting their natural functions. In addition, the study demonstrates that, in contrast to some earlier crystallographic evidence, bacterial membrane proteins are dynamic entities that respond to specific stimuli, rather than just passive pores.
This research was supported by the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health that supports basic biomedical research, and the National Science Foundation.
Jiang X et al. Ligand-Specific Opening of a Gated-Porin Channel in the Outer Membrane of Living Bacteria. Science. 1997;276:1261-4.
Dr. Phillip Klebba,
Department of Chemistry
University of Oklahoma, Norman
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