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Gram-negative bacteria shoot their way into cells

The bacteria that cause food poisoning, bubonic plague, and whooping cough all deploy the same weapon to infect the body. A molecular "syringe" sticks out of the bacteria, pokes a hole in a nearby cell, and squirts in venomous proteins that hijack the cell's machinery.

For the first time, Howard Hughes Medical Institute researchers have captured a detailed picture of the large doughnut-shaped base of the syringe barrel embedded in the bacterial membranes. The findings are reported in a paper in the June 2, 2005, issue of the journal Nature.

This first atomic picture of a major structural component of the hazardous molecular hypodermic may help scientists develop a new kind of drug that can disable the syringe and render disease-causing bacteria harmless while sparing beneficial bacteria. Currently, doctors must fight bacterial infections with antibiotics, which kill all bacteria, good and bad. Furthermore, the researchers are optimistic that drugs of this type might be effective against pathogens that are resistant to existing antibiotics.

"We believe this ring forms the foundation upon which all of the other components assemble," said senior author Natalie Strynadka, a HHMI international research scholar and associate professor of biochemistry at the University of British Columbia in Vancouver, Canada. "Without this assembly, there is no pathogenesis. This provides a real potential point of intervention."

The syringe is used almost exclusively by pathogenic bacteria, such as the Escherichia coli (E.coli) sometimes found in uncooked hamburgers, the Pseudomonas that cause life-threatening infections in the lungs of people with cystic fibrosis, and the plague bacillus, Yersinia pestis, that causes so-called black death. Many major plant pathogens also use the same piercing needle to puncture plant cells.

The barrel of the syringe spans the inner and outer membranes of Gram-negative bacteria, a major category of microbes that ha
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
1-Jun-2005


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