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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>