Scientists discover how Yersinia pestis avoids setting off immune system's early infection-alarm

Published on December 14, 2012 at 11:40 PM · No Comments

The plague-causing bacteria Yersinia pestis evades detection and establishes a stronghold without setting off the body's early alarms.

New discoveries reported this week help explain how the stealthy agent of Black Death avoids tripping a self-destruct mechanism inside germ-destroying cells.

The authors of the study, appearing in the Dec. 13 issue of Cell Host & Microbe, are Dr. Christopher N. LaRock of the University of Washington Department of Microbiology and Dr. Brad Cookson, UW professor of microbiology and laboratory medicine.

Normally, certain defender cells are programmed to burst if they are either invaded by or detect the presence of pathogens, Cookson explained. This host defense mechanism called pyroptosis ("going up in flames") eliminates places for the germs to reproduce. As it splits open, the cell spills a cauldron of antimicrobial chemicals and emits signals to alert of an attack and its precise location. Tissues become inflamed as more cells arrive to fight the infection.

The bacteria are widely believed to be behind the great pestilences of the Middle Ages in the 1300s. The pathogen had evolved a tactic to delay provoking people's protective inflammatory response until it was too late. Plague claimed an estimated 30 percent to 50 percent of Europe's 14th century population.

"People and pathogens have been in an eternal struggle since the dawn of humanity," Cookson said. With a hand over hand gesture he explained, "Humans continuously ratchet up their defenses, and germs repeatedly find a way around them."

During several medieval epidemics, the plague started in rats. High-jumping fleas transmitted it to and between humans. It commonly caused lymph nodes to rupture. Respiratory forms were more deadly. They damaged the lungs and were spread by sneezing. Plague bacteria in the blood stream ended lives through sepsis, in which the burden of infection overwhelms the body.

Today, the plague-causing bacteria are still circulating in the world. It is held at bay by sanitation measures and drug treatment.

Plague is now rare, with fewer than 15 infections annually in the United States. The number of cases outside the United States is significantly larger, but not precisely known. Plague therefore remains of scientific interest for several reasons.

The Yersinia survival strategy against the programmed death that could kill it and its host cell may offer ideas for vaccine development, Cookson said. At present, no vaccine exists against the plague. Yesinia is of concern as a potential biological warfare pathogen because it can be aerosolized and unsuspectingly breathed into the lungs. Vaccines are being sought to offer widespread public safety, as are methods for enhancing people's overall infection-fighting capacity.

Yersinia's techniques for modulating an inflammatory response also offer scientists an overarching perspective on a fundamental aspect of a variety of important diseases.

"Many medical problems stem from too much or too little inflammatory reaction," Cookson said. People who launch an insufficient inflammatory response, or whose inflammatory response is suppressed by medications, are prone to viral, bacterial and fungal infections.

"On the other hand, excessive or improperly regulated inflammatory responses are responsible for a large number of chronic conditions," Cookson said. These include vascular flare-ups leading to stroke or heart attack, and autoimmune diseases, among them lupus, juvenile diabetes, ulcerative colitis and myasthenia gravis. Severe injury also can promote life-threatening lung inflammation.

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