The germ that caused the plague epidemic that ravaged medieval Europe has a weakness that could help make a particularly dangerous form easier to treat, according to a study published on Thursday.
A bacterium known as Yersinia pestis causes both bubonic plague, the dreaded Black Death spread when people are bitten by an infected flea, and pneumonic plague, spread from one person to another through coughing or sneezing.There are periodic natural outbreaks of pneumonic plague like one that started in 2005 in the Democratic Republic of Congo. There also is acute concern terrorists could harness the bacterium as an airborne germ warfare agent to spread pneumonic plague.
Writing in the journal Science, scientists at Washington University School of Medicine in St. Louis said experiments with mice showed that the onslaught of the bacterium slows markedly when the germ cannot use a key protein.
Pneumonic plague can kill a person in three or four days after infection. Antibiotics can beat the bacterium, but by the time the infection becomes apparent the disease has progressed so far that it may be too late for them to do any good.
"It leaves a very narrow window of time that you could administer antibiotics and hope for good results," said William Goldman, the study's senior author.
Goldman said it might be possible to develop a drug that could slow progression of the disease so antibiotics can work.
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"It's easy to grow this bacterium. So I think there is a general concern that if someone really wanted to design a bioweapon, this is a candidate," said Goldman, professor of molecular microbiology at Washington University.
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The researchers developed a mouse model of the disease that mimicked human pneumonic plague.
It is a two-phase disease that begins with bacteria multiplying rapidly in the lungs, but with no symptoms.
About 36 hours after exposure, the disease progresses into a second phase, with a lot of inflammation and symptoms. Bacteria invade the spleen and other organs and an overwhelming, rapidly developing pneumonia proves fatal.
The researchers focused on a protein known as plasminogen activator, which they think the bacterium uses to break open protective blood clots that the body forms to try to limit the spread of an infection.
They made a mutant version of Yersinia without that protein. When mice were exposed to it, the bacterium managed to begin infection normally but the disease never progressed into the second phase and the mice were not dying from pneumonia.
The mice did eventually die, but it took much longer and probably resulted from a bloodstream infection.
Goldman said the study indicated this protein is essential for the normal progression of pneumonic plague, and that without it the disease stalls in the first phase, perhaps giving antibiotics time to work.
The protein is a type called a protease that breaks down other proteins. Drugs called protease inhibitors targeting these proteins have been used against other infectious diseases, including AIDS.
According to the World Health Organization, about 1,000 to 3,000 cases of plague are reported every year with 10 to 15 cases in the United States every year.
Source: Bio-Bio Technology
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