Mimic molecules to protect against plague

Bacteria that cause pneumonic plague can evade our first-line defences, making it difficult for the body to fight infection. In fact, a signature of the plague is the lack of an inflammatory response. Now, scientists have discovered a way to protect against death following infection with plague bacteria, by using molecules that can mimic the pathogens. According to research published in the July issue of Microbiology, these molecules make antibiotics more effective and can even be used to protect against other diseases.

The plague, caused by Yersinia pestis, has killed an estimated 200 million people worldwide. Although treatments have improved, it remains a threat to public health. It can be transmitted from human to human in aerosols and is therefore listed as a Category A bioterrorism agent.

"Yersinia pestis is successful in causing disease in mammals because it can dampen the normal non-specific immune response to infection," said Dr Scott Minnich from the University of Idaho, USA. "We found an intranasal therapy that stimulates the innate immune response and protects against pneumonic plague."

Following infection, lipid A (which is part of the bacterial surface) binds to receptors on our immune cells, triggering an immune response. Yersinia pestis circumvents this, stopping our cells from taking action. Molecules have been developed that mimic lipid A, eliciting a strong immune response that can prevent death in infected animals. Dr Minnich and his colleagues studied the effect of a nasal spray containing two such molecules, CRX-524 and CRX-527, on mice infected with Yersinia pestis.

"Treatment with synthetic modified lipid A molecules can directly protect animals against pneumonic plague infections," said Dr Minnich. "We also found that stimulating innate immunity using this nasal spray enhanced conventional antibiotic therapy. When it is given along with antibiotics, fewer doses and less antibiotic protects against pneumonic plague."

The results of this study suggest that synthetic modified lipid A compounds may provide a new therapeutic tool against plague infection. In a control group that did not receive the treatment, only 23% of mice survived for 3 days. When given the mimic molecules, up to 93% of mice survived for 3 days, 70% for 4 days and 34% recovered completely. This highlights the importance of the non-specific, first-line immune defences during the critical early phase of infection. Stimulating this response can over-ride a microorganism's counter measures to evade or disable the immune response.

Other studies have shown related therapeutic compounds are also effective against influenza and Listeria monocytogenes. "This work is still at a very basic animal model testing stage with regards to plague," said Dr Minnich. "What is exciting is that these studies provide insight into bacterial/host interactions in the disease process and promise new strategies to combat a variety of infectious agents."

Source: Society for General Microbiology

Related stories:

Researchers uncover attack mechanism of illness-inducing bacterium
An infectious ocean-dwelling bacterium found in oysters and other shellfish kills its host's cells by causing them to burst, providing the invader with a nutrient-rich meal, researchers at UT Southwestern Medical Center have found.
Symbiotic microbes induce profound genetic changes in their hosts
Though bacteria are everywhere — from the air we breathe and the food we eat to our guts and skin — the vast majority are innocuous or even beneficial, and only a handful pose any threat to us. What distinguishes a welcome microbial guest from an unwanted intruder?
Salmonella: Trickier than we imagined
Salmonella is serving up a surprise not only for tomato lovers around the country but also for scientists who study the rod-shaped bacterium that causes misery for millions of people.
Where man boldly goes, bacteria follow -- Are we contaminating space?
Life in outer space is an absolute certainty, and it is likely to be more familiar than we might think, according to an article in the May issue of Microbiology Today. Ever since the start of the space race we have sent more than just satellites and astronauts into space: spacecraft are not routinely decontaminated and are teeming with microbial life.
Researchers discover new strategies for antibiotic resistance
With infections increasingly resistant to even the most modern antibiotics, researchers at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) report in the September issue of Nature Reviews Microbiology on new clues they have uncovered in immune system molecules that defend against infection.
Scientists discover rare 'gene-for-gene' interaction that helps bacteria kill their host
Scientists have discovered that a cousin of the plague bacterium uses a single gene to out-fox insect immune defences and kill its host.
Researchers Uncover a Secret of the Black Death
Yersinia pestis, the bacteria that causes plague, is a sneaky little intruder with a remarkable ability to evade the body’s immune system. Upon entering an organism, Y. pestis employs a variety of strategies to slip below the radar of the innate immune response—the body’s front line of defense against invading pathogens—and in many cases kills the host before its more specific antibacterial response can develop.
Bacteria have their own immune system protecting against outside DNA
Bacteria like Salmonella have a complicated immune system that helps them recognize and isolate foreign DNA trying to invade their cell membrane, according to a University of Washington-led study in the June 8 issue of Science Express.

News discussion:

General Science news