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Novel plague virulence factor identified

n the blood of mammals. There are different forms of plague in humans -- bubonic, pneumonic and septicemic -- depending on site of infection; and infections in humans are highly lethal if not immediately treated.

"Dr Aballay has developed a new model for dissecting the ways pathogens such as the plague can infect and kill their hosts," said Pamela Marino, Ph.D., scientist at the National Institute of General Medical Science. "This creative approach should improve our ability to develop new medicines to treat such diseases."

Aballay has used the C. elegans, a worm commonly found in the soil, as a model to study the virulence mechanisms of other bacteria besides plague. The worm is an ideal model for genetic studies, he said, because it takes only three days to develop from an embryo to an adult capable of reproducing. Also, scientists can easily manipulate specific genes in the worm, and in contrast to other animal models, large quantities of the worms can be grown quickly and can even be frozen and used later.

"C elegans lives in the soil, so it continually comes into contact with bacteria and other microbes," Aballay said. "It has a highly developed system for not only recognizing bacteria, but also responding to them. The ability of its innate immune system to respond appropriately to specific bacteria is very similar to that of mammals."

Aballay tested Y. pestis in his model because another research team recently reported that the bacterium killed C. elegans by creating a "biofilm" over the worm's pharynx, causing it to die of starvation. Since mammals infected with Y. pestis do not die in this manner, Aballay believed that other virulence factors were involved in infecting the worm.

"We thought that a Y. pestis strain (known as KIM5) that lacks the genes (hmsHFRS operon) required for biofilm formation could still enter the worm's digestive system and eventually kill it by using a method different from food blockage," Aball
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Source:Duke University Medical Center


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