Scrapie could breach the species barrier

Scrapie is a neurodegenerative disease that has been known for centuries and which affects sheep and goats. Credit: INRA/Florent Giffard

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological state. In mice models reproducing the human species barrier, this prion induces a disease similar to Creutzfeldt-Jakob disease. These primary results published in Nature Communications on 16 December 2014, stress the necessity to reassess the transmission of this disease to humans.

Scrapie is a neurodegenerative disease that has been known for centuries and which affects sheep and goats. Similar to Bovine Spongiform Encephalopathy (BSE) or mad cow disease, scrapie is caused by a transmissible pathogen protein called prion.

However, and contrary to BSE[1], epidemiological studies have never been able to establish a link between this disease and the occurrence of prion diseases in humans. "Risks of transmitting scrapie to humans (zoonose) were hitherto considered negligible because of the species barrier that naturally prevents prion propagation between species," said Olivier 

Andreoletti, INRA scientist who led the present study.

Researchers at INRA studied the permeability of the human transmission barrier to pathogens responsible for scrapie, using animal models specifically developed for this purpose. This approach previously allowed the confirmation of the zoonotic nature of prions responsible for BSE in cows and of the variant of Creutzfeldt-Jakob disease in humans (vCJD).

Unexpectedly, in these rodent models, certain pathogens responsible for scrapie were able to cross the transmission barrier. Moreover, the pathogens that propagated through this barrier were undistinguishable from the prions causing the sporadic form of Creutzfeldt-Jakob disease (sCJD). This data suggest a potential link between the occurrence of certain sCJD and these animal prions.

"Since CJD is scarce, about 1 case per million and per year, and incubation periods are usually long -several decades- it is extremely difficult for epidemiological studies to try and make this link," explains Olivier Andreoletti.

In their conclusions, the authors stress the fact that CJD cases are rare though scrapie has been circulating for centuries in small ruminants for which we eat the meat. Even if in future studies scrapie is finally confirmed to have a zoonotic potential, the authors consider that this disease does not constitute a new major risk for public health.

Source: INRA-France

Nanotechnology against malaria parasites

After maturation, malaria parasites (yellow) are leaving an infected red blood cell and are efficiently blocked by nanomimics (blue). Credit: Fig: modified by University of Basel with permission from ACS

Malaria parasites invade human red blood cells, they then disrupt them and infect others. Researchers at the University of Basel and the Swiss Tropical and Public Health Institute have now developed so-called nanomimics of host cell membranes that trick the parasites. This could lead to novel treatment and vaccination strategies in the fight against malaria and other infectious diseases. Their research results have been published in the scientific journal ACS Nano.

For many infectious diseases no vaccine currently exists. In addition, resistance against currently used drugs is spreading rapidly. To fight these diseases, innovative strategies using new mechanisms of action are needed. The malaria parasite Plasmodium falciparum that is transmitted by the Anopheles mosquito is such an example. Malaria is still responsible for more than 600,000 deaths annually, especially affecting children in Africa (WHO, 2012).
Artificial bubbles with receptors

Malaria parasites normally invade human red blood cells in which they hide and reproduce. They then make the host cell burst and infect new cells. Using nanomimics, this cycle can now be effectively disrupted: The egressing parasites now bind to the nanomimics instead of the red blood cells.

Researchers of groups led by Prof. Wolfgang Meier, Prof. Cornelia Palivan (both at the University of Basel) and Prof. Hans-Peter Beck (Swiss TPH) have successfully designed and tested host cell nanomimics. For this, they developed a simple procedure to produce polymer vesicles -- small artificial bubbles -- with host cell receptors on the surface. The preparation of such polymer vesicles with water-soluble host receptors was done by using a mixture of two different block copolymers. In aqueous solution, the nanomimics spontaneously form by self-assembly.

Blocking parasites efficiently

Usually, the malaria parasites destroy their host cells after 48 hours and then infect new red blood cells. At this stage, they have to bind specific host cell receptors. Nanomimics are now able to bind the egressing parasites, thus blocking the invasion of new cells. The parasites are no longer able to invade host cells, however, they are fully accessible to the immune system.

The researchers examined the interaction of nanomimics with malaria parasites in detail by using fluorescence and electron microscopy. A large number of nanomimics were able to bind to the parasites and the reduction of infection through the nanomimics was 100-fold higher when compared to a soluble form of the host cell receptors. In other words: In order to block all parasites, a 100 times higher concentration of soluble host cell receptors is needed, than when the receptors are presented on the surface of nanomimics.

"Our results could lead to new alternative treatment and vaccines strategies in the future," says Adrian Najer first-author of the study. Since many other pathogens use the same host cell receptor for invasion, the nanomimics might also be used against other infectious diseases. The research project was funded by the Swiss National Science Foundation and the NCCR "Molecular Systems Engineering."

Source: University of Basel

Tree diseases can help forests

A healthy seedling of the tree Castilla elastica is on the left, while a dying seedling, attacked by a plant pathogen, is on the right. A study in the Journal of Ecology by University of Utah biologists shows that such tree diseases, while killing individual seedlings, can increase forest biodiversity. Credit: Erin Spear, University of Utah.

Plant diseases attack trees and crops and can hurt lumber and food production, but University of Utah biologists found that pathogens that kill tree seedlings actually can make forests more diverse.

While low rainfall has been blamed for a lack of drought-sensitive trees near the Pacific side of the Panama Canal, the new study answers a mystery about what keeps drought-tolerant trees from that area from living along the wetter Caribbean side of the canal. The answer: disease-causing plant pathogens, the researchers report in their study, published online Wednesday, Nov. 12 by the Journal of Ecology.

"Because seedlings of disease-sensitive tree species can't survive in the wetter forests and drought-sensitive tree species cannot survive in the drier forests, different tree species inhabit the wetter and drier forests even though they are only 30 miles apart" in Panama, says Phyllis Coley, a senior author of the study and a distinguished professor of biology.
In other words, tree pathogens contribute to the staggering diversity of trees in Panama's tropical forests, she adds.

The study's first author, biology doctoral student Erin Spear, says that is important because "conservation planning and predictions about how tree species distributions may shift with climate change require an understanding of the factors currently influencing where species can and cannot survive."

That is particularly important in tropical forests and other forests that are under elevated threat of deforestation.

Funding for the study came from Sigma Xi -- The Scientific Research Society, the Smithsonian Institution and the National Science Foundation.

Of Forests and Pathogens

Tropical forests are threatened, and dry tropical forests are even more threatened because sunnier, drier climates are better for growing crops and are favored by people. Some 90 percent of Panama's residents live on the nation's drier Pacific slope.

Forests are essential for feeding and sheltering animals, providing important medicines, storing carbon and water, and reducing erosion by holding soil in place. These functions are influenced by different species inhabiting a forest, so it is essential to understand why certain tree species can survive in certain areas but not others.

Panama's forests also are important economically because tree roots limit how much soil erodes into the Panama Canal, ensuring that huge container ships can pass. Researchers also believe the forests help maintain water levels in the canal because forest soil stores water, slowly releasing it into streams feeding the canal during the dry season.

Diversity is high in tropical forests. A 930-square-mile area bordering the Panama Canal has more than 800 tree species. By comparison, about half the state of Rhode Island -- or some 610 square miles -- is forested, and that area has only 51 tree species.

Part of the reason Panama's forests have more species is because the Pacific end of the canal receives less annual rainfall -- about 5.9 feet -- than the Caribbean end, where 9.8 feet of rain falls annually.

"While there is considerable evidence that less rain in the drier, Pacific forests means that drought-sensitive tree species can't survive there, it has been unclear what prevents the drought-tolerant species of the drier forests from living in the wetter forests," says University of Utah biology professor Tom Kursar, the study's other senior author. "Our study tackled that unanswered question."

So Spear braved mud, rain, insects and snakes to monitor seedlings of a variety of tree species in the wetter and drier forests of central Panama for pathogen-caused damage and death. Plant pathogens that make plants sick include bacteria, viruses and fungi.

Spear says the researchers' findings suggest that "all seedlings are at a greater risk of being injured and killed by pathogens in the wetter forests than in the drier forests." This could be because the damp environment of the wetter forests helps pathogens survive, and more rainfall helps pathogens move from one seedling to another.

But that's only half the story. Coley says that their study indicates "pathogens are implicated in the absence of the dry-forest tree species from the wetter forests, where they might otherwise be able to live. That is because dry-forest tree species are more likely to die from pathogen attack than wet-forest species."

Diagnosing Sick Seedlings

Spear collected the seeds for the study by hiking for miles, kayaking in the canal to collect fruit from overhanging branches, and even riding a crane-carried gondola more than 100 feet upward into the forest canopy.

She conducted the study at two forest sites in central Panama: one at the large Metropolitan Natural Park in Panama City on the drier Pacific side, and one on private property in the Santa Rita Ridge area on the wetter Caribbean side. She planted "gardens" of tree seeds -- including species typical of wetter and drier forests -- in 30 locations at each site. More than 1,000 seeds were planted; 725 of them sprouted.

Once the seeds were planted, the researchers covered them with wire mesh to protect the seeds and seedlings from being crushed by tree branches or eaten by animals.

Spear visited both sites weekly and took notes on the 725 seedlings. Weekly visits were essential because, diseased seedlings can be dead and decomposing within days.

"We monitored when the seeds germinated, the occurrence of and date when symptoms of pathogen attack were observed, if and when a seedling died, and we ascribed a cause of death," Spear says. Pathogen symptoms included patches of black, dead tissue in the leaves or stem. "In some cases, we could actually see the pathogen growing on the seedling," she says.

Of the 725 seedlings that germinated, 38 percent suffered pathogen-caused damage, including 11 percent of seedlings killed by pathogens.

Compared with seedlings in the drier forest, seedlings in the wetter forest were 74 percent more likely to suffer pathogen-caused damage and 65 percent more likely to be killed by pathogens.

"But what was really striking was that pathogen-caused damage was five times more likely to be lethal for seedlings of dry-forest species than for wet-forest species," suggesting dry- and wet-forest species differ in their ability to halt or slow infection, Spear says.

The researchers next plan to identify specific fungi, bacteria and other pathogens and whether they differ in wetter and drier forests.

During her study at the drier park site in Panama City, Spear discussed her research with tourists and other park visitors.

"I'd emerge from the tangles of vines sweaty, muddy and generally disheveled and people couldn't help but ask what I was doing," Spear recalls. "It was heartening to hear how the forest had touched these very different people."

A brief time-lapse video of a seedling dying from pathogen attack during a period of several days can be seen at: http://vimeo.com/58026978 Video by Erin Spear, University of Utah.


Source: University of Utah