Atlanta (September 28, 2005) — Researchers at the GeorgiaInstitute of Technology and the John Innes Centre in the United Kingdomhave uncovered a mechanism with which disease-causing bacteria maythwart the body’s natural defense responses. The findings, which couldultimately lead to the development of more effective antibiotics,appear in the September 29, 2005 issue of the journal Nature.
“Nitricoxide is produced by the body to fight infections. We discovered amechanism that allows bacterial cells to detect nitric oxide and turnit into something that’s harmless to the cell,” said Stephen Spiro,associate professor in the School of Biology at Georgia Tech.
Spiro,along with colleagues Benoît D'Autréauz, Nicholas Tucker and Ray Dixonfrom the John Innes Centre, studied a non-pathogenic strain ofEscherichia coli, which is very closely related to salmonella bacteria.
Thepathogenic forms of E. coli and salmonella are usually transmitted tohumans through undercooked meat, unwashed vegetables and crosscontamination from surfaces on which these foods were prepared.Infections from either of these organisms can cause diarrhea, abdominalcramps and sometimes more serious illnesses that requirehospitalization. E.coli doesn’t respond well to antibiotics, whilesalmonella has developed several drug-resistant strains. Learning howthe bacteria handle the body’s immune response is the first step indeveloping more effective medicines.
Spiro and colleagues focusedtheir study on the NorR protein and the role it plays in reducing thelevels of nitric oxide. In response to nitric oxide, NorR binds to DNAin order to regulate expression of an enzyme that reduces the amount ofnitric oxide in the bacteria. Since nitric oxide binds to metals, theresearchers suspected that there might be a metal in the protein.
“Itturns out that the protein NorR contains a single molecule of iron,”said Spiro. “Our study found that the nitric oxide binds to the iron,which in turn activates the protein.”
Once activated, the proteincontrols expression of the norVW genes. These genes encode an enzymethat removes the nitric oxide, allowing the bacteria to fend off thebody’s defenses.
The discovery of this mechanism is just thefirst step in what Spiro hopes will be a line of research aimed atdisrupting the mechanism by which the bacteria rids itself of thepoisonous nitric oxide.
“If we can interfere with the mechanism, it could lead to better antibiotics and better treatments,” said Spiro.
The research was funded by a grant from the Biotechnology and Biological Sciences Research Council.
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