Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bubonic Bottleneck: UNC Scientists Overturn Dogma on the Plague

16.02.2015

The current outbreak of the plague in Madagascar shines a light on the need for new approaches to treat the ancient pathogen. A new UNC study unexpectedly unravels a long-held theory on how a fleabite leads to infection.

For decades, scientists have thought the bacteria that cause the bubonic plague hijack host cells at the site of a fleabite and are then taken to the lymph nodes, where the bacteria multiply and trigger severe disease. But UNC School of Medicine researchers discovered that this accepted theory is off base. The bacteria do not use host cells; they traffic to lymph nodes on their own and not in great numbers.


National Institute of Allergies and Infectious Diseases

Yersinia Pestis, the bacteria that cause the plague

In fact, most of the plague-causing bacteria – called Yersinia pestis – get trapped in a bottleneck either in the skin, while en route to the lymph node, or in the node itself. Only a few microbes break free to infect the lymph node and cause disease.

“Anytime you find something where the host is winning, you want to exploit it,” said Virginia Miller, PhD, professor of microbiology and immunology and senior author of the paper in PLoS Pathogens. “If we can understand how the host and the bacteria contribute to this bottleneck, then this could become something we’d target so we could either ramp up what’s causing the bottleneck or slow down the infection.”

The discovery offers much needed information about how virulent insect-borne diseases, such as plague, malaria, and dengue virus cause infection. The findings also present new routes for research on how bacterial strains cause disease despite the immune system’s best efforts.

The plague, which killed millions of people during the Middle Ages, is contracted by several people each year in the western United States. Outbreaks have occurred in the recent past in India and Africa, and one is unfolding right now in Madagascar. Standard antibiotics are effective against Y. pestis if taken early enough. But infection can go undetected for days, making diagnosis difficult and antibiotics less effective the longer the bacteria take root.

There are three kinds of plague all caused by Y. pestis: bubonic, which is contracted through fleabite; pneumonic, which is contracted by breathing in the bacteria; and septicemic, which is a severe infection of blood.

Miller’s team studies the pneumonic and bubonic versions. Three years ago, Rodrigo Gonzalez, PhD – a UNC graduate student at the time and now a postdoctoral fellow at Harvard – searched the scientific literature for data confirming the accepted notion that Y. pestis gets trafficked by human phagocytic cells from the fleabite site to the lymph nodes. Scientists readily accepted this idea because when Y. pestis microbes are added to phagocytic cells in culture, the cells do soak up the bacteria.

Phagocytes essentially eat harmful microbes, and because these cells traffic through the lymphatic system, scientists came to the logical conclusion that phagocytes take the Y. pestis to the lymph nodes.

But Gonzales and Miller knew that a fleabite does not penetrate all layers of skin like an injection does. The bites of fleas and mosquitos are intradermal; they occur within the layers of skin. Gonzales and Miller agreed that testing this long-held theory was a worthy project.

Gonzales spent months developing an accurate way to mimic the flea bite in the lab so that the proper amount of bacteria would get transferred into the skin of mice. Then Miller’s team created 10 special DNA sequences and added them to the chromosome of Y. pestis to generate 10 different strains. This did not affect virulence of the bacteria but allowed Miller’s team to tag the microbes so that the researchers could identify which bacteria traveled from the “bite site” to the lymph nodes.

“We found that only one or two of the 10 bacteria made it to the lymph node,” Miller said. “But they got there fast – within five or ten minutes after the bacteria were introduced. We know that if a bacterium is traveling in a host cell, it would not move that fast because host cells are slow; they kind of crawl through the lymphatic system instead of flowing through fluid like bacteria can.”

Miller’s team is currently conducting experiments to figure out how most of the bacteria are prevented from infecting the lymph node.

“We may have found a point of vulnerability,” Miller said. “Exploiting it could lead to new ways to defeat Yersinia pestis and other insect-borne pathogens.”

The National Institutes of Health and the Robert D. Watkins Fellowship from American Society for Microbiology funded this research.

Contact Information
Mark Derewicz
Science Communications Manager
mark.derewicz@unch.unc.edu

Mark Derewicz | newswise
Further information:
http://www.med.unc.edu/

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>