Mimic molecules to protect against plague

July 03, 2008

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."
-end-


Microbiology Society

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.