Labslink Research News

Scientists characterize protein essential to survival of malaria parasite

Fri, 06 Jan 2012 17:07:01 PDT

A biology lab at Washington University has just cracked the structure and function of a protein that plays a key role in the life of a parasite that killed 655,000 people in 2010........> Full story

Parasite uses the power of sexual attraction to trick rats into becoming cat food

Fri, 19 Aug 2011 18:17:34 PDT

When a male rat senses the presence of a fetching female rat, a certain region of his brain lights up with neural activity, in anticipation of romance. Now Stanford University researchers have discovered that in male rats infected with the parasite Toxoplasma, the same region responds just as strongly to the odor of cat urine. Is it time to dim the lights and cue the Rachmaninoff for some cross-species canoodling? "Well, we see activity in the pathway that normally controls how male rats respond to female rats, so it's possible the behavior we are seeing in response to cat urine is sexual attraction behavior, but we don't know that," said Patrick House, a PhD candidate in neuroscience in the School of Medicine. "I would not say that they are definitively attracted, but they are certainly less afraid. Regardless, seeing activity in the attraction pathway is bizarre." For a rat, fear of cats is rational. But a cat's small intestine is the only environment in which Toxoplasma can reproduce sexually, so it is critical for the parasite to get itself into a cat's digestive system in order to complete its lifecycle. Thus it benefits the parasite to trick its host rat into putting itself in position to get eaten by the cat. No fear, no flight – and kitty's dinner is served. House, the lead author of a paper about the research published in the Aug. 17 issue of PLoS ONE, works in the lab of Robert Sapolsky, a professor of biology and, at the medical school, of neurology and neurological sciences. Scientists have known about Toxoplasma's manipulation of rats for years and they knew that rats infected with Toxoplasma seemed to lose their fear of cats. It is an example of what is called the "manipulation hypothesis," which holds that some parasites alter the behavior of their host organism in a way that benefits the parasite. There are several known examples of the phenomenon in insects. But the details of how the little single-celled protozoan Toxoplasma, about a hundredth of a millimeter long, exerts control over the far more sophisticated rat have been a mystery. Sapolsky's group previously determined that although the parasite infects the entire brain, it shows a preference for a region of the brain called the amygdala, which is associated with various emotional states. Once in the brain, the parasite forms cysts around itself, in which it essentially lies dormant. House was interested in how the amygdala is affected by the parasite, so he ran a series of experiments with both healthy and Toxoplasma-infected rats. He exposed each male rat to either cat urine or a female rat in heat for 20 minutes before analyzing its brains for evidence of excitation in the amygdala. For the experiments, he used cat urine he purchased in bulk from a wholesaler. No actual cats participated in the experiments. House analyzed certain subregions of the amygdala that focus on innate fear and innate attraction. In healthy male rats, cat urine activated the "fear" pathway. But in the infected rats, although there was still activity in the fear pathway, the urine prompted quite a bit of activity in the "attraction" pathway as well. "Exactly what you would see in a normal rat exposed to a female," House said. "Toxoplasma is altering these circuits in the amygdala, muddling fear and attraction," he said. The findings confirmed observations House made during the experiments, when he noticed that the infected rats did not run when they smelled cat urine, but actually seemed drawn to it and spent more time investigating it than they would just by chance. Although House doesn't have the data yet to speculate on just how the cysts in the rats' brains are causing the behavioral changes, he is impressed with what Toxoplasma can accomplish. "There are not many organisms that can get into the brain, stay there and specifically perturb your behavior," he said. "In some ways, Toxoplasma knows more about the neurobiology of fear than we do, because it can specifically alter it," Sapolsky said. Because Toxoplasma reproduces in the small intestine of cats, the parasites are excreted in feces, which is presumably how rats get infected. Rats are known to be extremely curious, tasting almost everything they come in contact with. Toxoplasma is also frequently found in fertilizer and can infect virtually any mammal. Approximately one third of the world's human population is infected with Toxoplasma. For most people, it appears to present no danger, although it can be fatal in people with compromised immune systems. It also can cross the placental barrier in a pregnant woman and lead to many complications, which is why pregnant women are advised not to clean cat litter boxes. House said humans acquire the parasite by eating undercooked meat or "eating little bits of cat poop, which I suspect happens more often than people want to admit." Or know. Although Toxoplasma has not been shown to have any ill effects in most people, one can't help but wonder whether it truly has no effect in humans. "There are a couple dozen studies in the last few years showing that if you have schizophrenia, you are more likely to have Toxoplasma. The studies haven't shown cause and effect, but it's possible," House said. "Humans have amygdalae too. We are afraid of and attracted to things – it's similar circuitry."

Comparison of genomes of plant parasites provides solid clues for response

Mon, 16 May 2011 17:46:19 PDT

As plant scientists unravel the genomes of plant pathogens, comparisons can be made of the different and not-so-different invasion strategies for the organisms that threaten crops. John McDowell, associate professor of plant pathology at Virginia Tech, points out similarities in the strategies of several devastating rusts and mildew. Based on his own research and the published findings of other scientists, McDowell observes shared traits that different microbes have evolved to survive as absolutely dependent on their hostile hosts – and that can be targeted to turn on crop plant's resistance. McDowell's comparison of three research articles about the defensive strategies of fungi and oomycetes (fungus-like microbes) that cause plant disease appears as an invited Commentary in the Proceedings of the National Academy of Sciences (PNAS) early edition published online the week of May 16. Sebastien Duplessis of Nancy University, Champenoux, France, and his colleagues describe the genome of the organisms that cause stem rust of wheat and barley, leaf rust of poplar in an article* in the same issue of PNAS in which McDowell's Commentary appears. McDowell compares this work with two articles that appeared in the journal Science in 2010** that looked at adaptations strategies of powdery mildew and downy mildew. One of these articles reports the sequencing of the genome of the pathogen that causes powdery mildew by an international group that included McDowell and other Virginia Tech scientists (http://www.vtnews.vt.edu/articles/2010/12/120910-vbi-mildew.html). Commonalities between the rust and mildew pathogens include the ability to keep a low profile by reducing the release of toxins that will elicit a response from the host's immune system and secreting molecules called effector proteins that sabotage the immune response in the host. While questions remain, such as whether effector proteins contribute to alteration of cell structure and metabolism in the host plant, "It's important to know your enemies and the genomes of these devastating parasites have provided some important insights into the strategies that they use to sabotage the plant's immune responses," said McDowell. "It is now possible to translate pathogen genome data into better tools for diagnosis and disease forecasting. And by comparing the genomes of pathogens that infect different types of crops, we and other plant pathology researchers are developing and testing new ideas for breeding crops with stronger disease resistance genes." McDowell's research is supported by the National Science Foundation and the U.S. Department of Agriculture.

Insight into parasite family planning could help target malaria

Wed, 16 Mar 2011 07:14:50 PDT

Fresh insight into the way the parasite that causes malaria reproduces could lead to new treatments to help curb the spread of the disease. Scientists studying the disease have found that upsetting the parasite's reproductive strategy could prevent infections from transmitting from person to person. Researchers at the Universities of Edinburgh and Oxford examined the parasite at a stage of its development in which it produces male and female forms in the bloodstream of its victims. These parasites then breed inside mosquitoes to produce fresh offspring that are transmitted when the insects feed on other people or animals. The study showed that killing either the male or female forms was ineffective at stopping the spread of the disease, because the parasites replace those which are lost. However, the researchers were able to overcome this by damaging the male and female forms instead of killing them. This meant that although the parasites were able to reproduce, their offspring did not survive. Malaria affects people and animals and is spread by the bite of the mosquito. The disease kills approximately one million people each year, mainly children in sub-Saharan Africa, and affects hundreds of millions more. The study, published in PLoS Pathogens, was funded by the Portuguese Foundation for Science and Technology, the Royal Society, Balliol College Oxford and the Wellcome Trust. Ricardo Ramiro, of the University of Edinburgh's School of Biological Sciences, who took part in the study, said: "Our studies show that inflicting just the right amount of damage could be the best way to interrupt the malaria parasite's development in the mosquito and help prevent the spread of disease."

Virus, parasite may combine to increase harm to humans

Fri, 11 Feb 2011 03:27:24 PDT

A parasite and a virus may be teaming up in a way that increases the parasite’s ability to harm humans, scientists at the University of Lausanne in Switzerland and Washington University School of Medicine in St. Louis report this week in Science. When the parasite Leishmania infects a human, immune system cells known as macrophages respond. However, some Leishmania strains are infected with a virus that can trigger a severe response in macrophages, allowing the parasite to do more harm in animal infections. In humans, the parasite's viral infection may be why some strains of Leishmania in Central and South America tend to cause a disfiguring form of disease that erodes the soft tissues around the nose and mouth.......> Full story

Malaria parasite caught red-handed invading blood cells

Thu, 20 Jan 2011 03:25:21 PDT

Australian scientists using new image and cell technologies have for the first time caught malaria parasites in the act of invading red blood cells. The researchers, from the Walter and Eliza Hall Institute in Melbourne, Australia, and the University of Technology, Sydney (UTS), achieved this long-held aim using a combination of electron, light and super resolution microscopy, a technology platform new to Australia. The detailed look at what occurs as the parasite burrows through the walls of red blood cells provides new insights into the molecular and cellular events that drive cell invasion and may pave the way for developing new treatments for malaria. Institute researchers Dr Jake Baum, Mr David Riglar, Dr Dave Richard and colleagues from the institute's Infection and Immunity division led the research with colleagues from the i3 institute at UTS. Dr Baum said the real breakthrough for the research team had been the ability to capture high-resolution images of the parasite at each and every stage of invasion, and to do so reliably and repeatedly. Their findings are published in today's issue of the journal Cell Host & Microbe. "It is the first time we've been able to actually visualise this process in all its molecular glory, combining new advances developed at the institute for isolating viable parasites with innovative imaging technologies," Dr Baum said. "Super resolution microscopy has opened up a new realm of understanding into how malaria parasites actually invade the human red blood cell. Whilst we have observed this miniature parasite drive its way into the cell before, the beauty of the new imaging technology is that it provides a quantum leap in the amount of detail we can see, revealing key molecular and cellular events required for each stage of the invasion process." The imaging technology, called OMX 3D SIM super resolution microscopy, is a powerful new 3D tool that captures cellular processes unfolding at nanometer scales. The team worked closely with Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull from the i3 institute at UTS to capture these images. "This is just the beginning of an exciting new era of discoveries enabled by this technology that will lead to a better understanding of how microbes such as malaria, bacteria and viruses cause infectious disease," Associate Professor Whitchurch said. Dr Baum said the methodology would be integral to the development of new malaria drugs and vaccines. "If, for example, you wanted to test a particular drug or vaccine, or investigate how a particular human antibody works to protect you from malaria, this imaging approach now gives us a window to see the actual effects that each reagent or antibody has on the precise steps of invasion," he said. Malaria is caused by the Plasmodium parasite, which is transmitted by the bite of infected mosquitoes. Each year more than 400 million people contract malaria, and as many as a million, mostly children, die. "Historically it has been very difficult to both isolate live and viable parasites for infection of red blood cells and to employ imaging technologies sensitive enough to capture snapshots of the invasion process with these parasites, which are only one micron (one millionth of a metre) in diameter," Dr Baum said. He said one of the most interesting discoveries the imaging approach revealed was that once the parasite has attached to the red blood cell and formed a tight bond with the cell, a master switch for invasion is initiated and invasion will continue unabated without any further checkpoints. "The parasite actually inserts its own window into the cell, which it then opens and uses to walk into the cell, which is quite extraordinary," Dr Baum said. "Visually tracking the invasion of Plasmodium falciparum into a red blood cell is something I've been aiming at ever since I began at the Walter and Eliza Hall Institute in 2003; it's really thrilling to have reached that goal. This technology enables us to look at individual proteins that we always knew were involved in invasion, but we never knew what they did or where they were, and that, we believe, is a real leap for malaria researchers worldwide."

Malaria parasite caught red-handed invading blood cells

Thu, 20 Jan 2011 03:24:56 PDT

Study sheds new light on river blindness parasite

Thu, 13 Jan 2011 03:31:33 PDT

The team found that a bacterium inside the worm acts as a 'disguise' for the parasite, resulting in the immune system reacting to it in an ineffective way. The bacteria protect the worm from the body's natural defences, but once the bacteria are removed with antibiotics, the immune system responds appropriately, releasing cells, called eosinophils, that kill the worm. Antibiotics are successful against the parasite, but the long treatment regime means that it has limited use across whole communities. These new findings suggest that if medics could prime the immune system to recognise the worm, a shorter duration of antibiotic treatment may be sufficient to overcome its bacterial defences. River Blindness is caused by black flies that breed in rivers and deposit the larvae of a worm into the person they bite. The infection leads to severe itching of the skin and lesions of the eye which can result in blindness. It affects millions of people in developing countries, particularly in West and Central Africa. A closely related parasite also infects cattle, which causes lumps to appear on the animal's skin but does not cause blindness or other illness. Dr Ben Makepeace, from the University's Institute of Infection and Global Health, explains: "Our team has already shown that removing the bacteria with antibiotics results in the death of the worm, but until now we were unaware of how the bacteria protected the parasite in the first instance. Antibiotics can rid the parasite of the bacteria, allowing the immune system to respond properly, but it is a long treatment process, lasting up to six weeks. "Now we can begin to look for a way to 'prime' the body into reacting to the parasite more efficiently. Currently there is no vaccine for River Blindness, but if a candidate could be identified this may help boost the immune system ahead of antibiotic treatment and reduce the length of time patients have to take the drug. It is essential that whole communities are cured of the infection and the more we know about the mechanisms the parasite uses to survive in the body, the further we can progress with finding a practical treatment that kills adults worms and not just the larval stages"

MIT researchers study the danger of toxoplasma parasites

Wed, 05 Jan 2011 03:40:22 PDT

About one-third of the human population is infected with a parasite called Toxoplasma gondii, but most of them don't know it. Though Toxoplasma causes no symptoms in most people, it can be harmful to individuals with suppressed immune systems, and to fetuses whose mothers become infected during pregnancy. Toxoplasma spores are found in dirt and easily infect farm animals such as cows, sheep, pigs and chickens. Humans can be infected by eating undercooked meat or unwashed vegetables. Jeroen Saeij, an assistant professor of biology at MIT is investigating a key question: why certain strains of the Toxoplasma parasite (there are at least a dozen) are more dangerous to humans than others. He and his colleagues have focused their attention on the type II strain, which is the most common in the United States and Europe, and is also the most likely to produce symptoms. In a paper appearing in the Jan. 3 online edition of the Journal of Experimental Medicine, the researchers report the discovery of a new Toxoplasma protein that may help explain why type II is more virulent than others. Toxoplasma infection rates vary around the world. In the United States, it's about 10 to 15 percent, while rates in Europe and Brazil are much higher, around 50 to 80 percent. However, these are only estimates — it is difficult to calculate precise rates because most infected people don't have any symptoms. After an infection is established, the parasite forms cysts, which contain many slowly reproducing parasites, in muscle tissue and the brain. If the cysts rupture, immune cells called T cells will usually kill the parasites before they spread further. However, people with suppressed immune systems, such as AIDS patients or people undergoing chemotherapy, can't mount an effective defense. "In AIDS patients, T cells are essentially gone, so once a cyst ruptures, it can infect more brain cells, which eventually causes real damage to the brain," says Saeij. The infection can also cause birth defects, if the mother is infected for the first time while pregnant. (If she is already infected before becoming pregnant, there is usually no danger to the fetus.) There are drugs that can kill the parasite when it first infects someone, but once cysts are formed, it is very difficult to eradicate them. A few years ago, Saeij and colleagues showed that the Toxoplasma parasite secretes two proteins called rhoptry18 and rhoptry16 into the host cell. Those proteins allow the parasite to take over many host-cell functions. In the new study, the MIT team showed that the parasite also secretes a protein called GRA15, which triggers inflammation in the host. All Toxoplasma strains have this protein, but only the version found in type II causes inflammation, an immune reaction that is meant to destroy invaders but can also damage the host's own tissues if unchecked. In the brain, inflammation can lead to encephalitis. This ability to cause inflammation likely explains why the type II strain is so much more hazardous for humans, says Saeij. Saeij and his team, which included MIT Department of Biology graduate students Emily Rosowski and Diana Lu, showed that type II GRA15 leads to the activation of the transcription factor known as NF-kB, which eventually stimulates production of proteins that cause inflammation. The team is now trying to figure out how that interaction between GRA15 and NF-kB occurs, and why it is advantageous to the parasite. Ultimately, Saeij hopes to figure out how the parasite is able to evade the immune system and establish a chronic infection. Such work could eventually lead to new drugs that block the parasite from establishing such an infection, or a vaccine that consists of a de-activated form of the parasite.

Protein helps parasite survive in host cells

Wed, 29 Dec 2010 03:24:22 PDT

Researchers at Washington University School of Medicine in St. Louis have learned why changes in a single gene, ROP18, contribute substantially to dangerous forms of the parasite Toxoplasma gondii. The answer has likely moved science a step closer to new ways to beat Toxoplasma and many other parasites. In a study published in Cell Host & Microbe, scientists show that the ROP18 protein disables host cell proteins that would otherwise pop a protective bubble the parasite makes for itself. The parasite puts the bubble on like a spacesuit by forming a membrane around itself when it enters host cells. This protects it from the hostile environment inside the cell, which would otherwise kill it. “If we can find therapies that block ROP18 and other parasite proteins like it, that could give the host the upper hand in the battle against infection,” says first author Sarah Fentress, a graduate student in the laboratory of L. David Sibley, PhD, professor of molecular microbiology. Infection with Toxoplasma, or toxoplasmosis, is most familiar to the general public from the recommendation that pregnant women avoid changing cat litter. Cats are commonly infected with the parasite, as are some livestock and wildlife. “The exact role of ROP18 and related proteins in human disease remains to be studied,” says Sibley. “But mice are natural hosts of Toxoplasma, so studies in laboratory mice are relevant to the spread of infection.” Epidemiologists estimate that as many as one in every four humans is infected with Toxoplasma. Infections typically cause serious disease only in patients with weakened immune systems. In some rare cases, though, infection in patients with healthy immune systems leads to serious eye or central nervous system disease, or congenital defects or death in the fetuses of pregnant women. In the new study, Fentress showed that the ROP18 protein binds to a class of host proteins known as immunity-related GTPases. Tests in cell cultures and animal models showed that this binding leads to a reaction that disables the GTPases, which normally would rupture the parasite's protective membrane. “With one exception, humans don’t have the same family of immunity-related GTPases,” Fentress notes. “But we do have a similar group of immune recognition proteins called guanylate-binding proteins, and we are currently testing to see if ROP18 deactivates these proteins in human cells in a similar manner.” The findings could be applicable to other parasites and pathogens. Toxoplasmosis belongs to a family of parasites that includes the parasite Plasmodium, which causes malaria. All surround themselves with protective membranes when they enter host cells. “Plasmodium doesn’t make ROP18, but it does secrete related proteins called FIKK,” says Fentress. “It’s possible they also act to thwart host defense mechanisms like GTPases and guanylate-binding proteins.”

Researchers unlock how key drug kills tropical parasites

Thu, 11 Nov 2010 03:27:05 PDT

In a major breakthrough that comes after decades of research and nearly half a billion treatments in humans, scientists have finally unlocked how a key anti-parasitic drug kills the worms brought on by the filarial diseases river blindness and elephantitis. Understanding how the drug ivermectin works has the potential to lead to new treatments for the diseases, in which the body is infected with parasitic worms, said Charles Mackenzie, a professor of veterinary pathology in the College of Veterinary Medicine and researcher on the project. The diseases afflict about 140 million people worldwide, doing much of their damage in equatorial Africa. "Ivermectin is one of the most important veterinary and human anti-parasitic agents ever," Mackenzie said. "Knowing specifically how it interacts with the body's own immune system and kills parasitic worms opens up whole new treatment avenues." The research appears in the current edition of the Proceedings of the National Academy of Sciences. Elephantiasis (lymphatic filariasis) is caused by tiny worms spread via mosquitoes and results in severe swelling of the legs, arms and torso. River blindness (onchocerciasis) is spread by black flies, and after the worms die in a person's eye, they can cause blindness and debilitating skin disease. Ivermectin works by killing the first stage of the worm in the human body, and also appears to paralyze the reproductive tract of the adult female worms, stopping reproduction of new parasites. What the researchers discovered is that the drug does this by preventing the worm from secreting proteins through a pore in its mid-body; ivermectin binds to receptors at the pore and blocks the secretions. It is the secretions that normally block a person's ability to attack and kill the worm; after the drug prevents them, the host's own immune system is able to attack and kill the parasites. "Understanding how the worms were avoiding the host's immune responses will greatly enhance our ability to manipulate the immune system to the advantage of the host, and perhaps develop vaccines," Mackenzie said. "Also, one of the most important challenges in the overall effort against filarial infections relates to the development of resistance and the loss of efficacy of the drugs we use; this new knowledge provides an important key to understanding and perhaps preventing resistance." Ivermectin was developed by pharmaceutical firm Merck & Co. in the 1970s. It was donated in 1987 for use to treat river blindness, as existing drugs were in fact inducing blindness. Ivermectin was able to be used safely in mass drug administration programs in many developing countries, shifting the paradigm for how public health programs delivered medicines in rural areas. The drug then was used in other parasitic disease programs, such as the one for elephantiasis, treating more than 100 million people for that disease. Mackenzie has worked for more than 20 years on tropical filarial diseases, much of that time partnering with Tim Geary at McGill University in Montreal. Geary's lab was critical in the ivermectin findings, as was McGill graduate student Yovany Moreno. Geary and Mackenzie also recently were awarded $2 million from the Gates Foundation to study another anti-filarial drug, flubendazole.

Scientists pinpoint key defense against parasite infection

Tue, 09 Nov 2010 03:21:45 PDT

Scientists have made a significant discovery about how the body defends itself against snail fever, a parasitic worm infection common in developing countries. Researchers studied the immune response in mice infected with snail fever parasites. They found that a particular type of immune cell, known as the dendritic cell, is responsible for triggering the immune system's defence against the invading parasite. The development, by scientists at the University of Edinburgh, could point towards new avenues of research into treatments for the condition, which causes long-term infection. Snail fever, also known as bilharzia, is a water-borne potentially fatal disease caused by flukes – or parasitic worms – found in freshwater snails in the tropics. Common in developing countries in Asia, Africa and South America, the condition causes chronic illness that can damage internal organs and impair growth and brain development in children. The disease, which commonly affects tourists who kayak or swim in infected waters, is second only to malaria in terms of its devastating social and economic impact. The study, published in the Journal of Experimental Medicine, was carried out in collaboration with the German Cancer Research Centre in Heidelberg and funded by the Medical Research Council and the Wellcome Trust. Dr Andrew MacDonald, of the University of Edinburgh's School of Biological Sciences, who led the research, said: "Until now, we were unsure which of the many cells found in the immune system were crucial to fighting this parasite. We now know that dendritic cells are key to the process. If we can manipulate this immune response, we stand a chance of targeting the widespread suffering and chronic illness caused by this infection."

Paradise lost -- and found

Fri, 29 Oct 2010 03:19:18 PDT

Ancient gardens are the stuff of legend, from the Garden of Eden to the Hanging Gardens of Babylon. Now researchers at Tel Aviv University, in collaboration with Heidelberg University in Germany, have uncovered an ancient royal garden at the site of Ramat Rachel near Jerusalem, and are leading the first full-scale excavation of this type of archaeological site anywhere in the pre-Hellenistic Levant.

According to Prof. Oded Lipschits and graduate student Boaz Gross of Tel Aviv University's Department of Archaeology, this dig is an unparalleled look into the structure and function of ancient gardens. "We have uncovered a very rare find," says Prof. Lipschits, who believes that this excavation will lead to invaluable archaeological knowledge about ancient royal gardens in the Middle East.......> Full story

How parasites react to the mouse immune system may help to shape their control

Wed, 20 Oct 2010 03:24:59 PDT

How parasites use different life-history strategies to beat our immune systems may also provide insight into the control of diseases, such as elephantiasis and river blindness, which afflict some of the world's poorest communities in tropical South-East Asia, Africa and Central America. The research is due to be published next week in the online, open-access journal PLoS Biology. The study, led by Dr Simon Babayan of the University of Edinburgh, showed using a mouse model of parasite infection (for diseases such as elephantiasis) that when the parasitic worms enter the body, they are potentially able to adjust their survival strategy relative to the strength of the host's immune system. When the immune reaction is strong, the parasites accelerate their growth rate to produce offspring earlier and in greater numbers, ensuring the continued spread of the disease. The authors note that additional work will be required to confirm whether such a response is adaptive and to tease out the mechanisms involved. Elephantiasis, which causes swelling of the legs, and river blindness, are both caused by parasitic worms spread by black flies and mosquitoes. No vaccines for these conditions currently exist. Those affected can be left disfigured, vulnerable to illness, and unable to work, thus putting economic strain on affected societies. The Edinburgh team will contribute their latest findings into an international project to create a vaccine that, when complimented by drug treatments, could help to eliminate these diseases. Dr Babayan said: "Most vaccines mimic the natural immunity of people, but our research suggests this approach could be counterproductive for some parasitic diseases. We hope this latest finding will help inform the design of future vaccines against these infections Clinical trials analyse the impact of potential vaccines on host health; we suggest they should also focus on their impact on parasite life history."

NIH grantees find metabolic pathway in malaria parasites; possible drug targets

Thu, 05 Aug 2010 03:56:07 PDT

A newly described metabolic pathway used by malaria-causing parasites may help them survive inside human blood cells. The finding, by researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, clarifies the picture of parasite metabolism and provides clues to potential weak points in the pathway that might be attacked with drugs. In most living things, several major chemical processes involved in converting food to energy are linked through a cyclic hub called the tricarboxylic acid cycle, also known as the Krebs cycle. NIAID grantee Manuel Llinás, Ph.D., of Princeton University, and his colleagues discovered that Plasmodium falciparum, the deadliest malaria parasite, uses a double-branched metabolic pathway instead of the classical loop. According to Dr. Llinás, this specific branched pathway has not been detected previously in any other organism. The malaria parasite appears to use one branch primarily to generate the molecule acetyl-CoA, which it needs to thrive within a host organism. This branch may represent particularly vulnerable spots to target with anti-malarial drugs, says Dr. Llinás. The detailed description of the chemical steps involved in the metabolic pathway of the malaria parasite also could aid future malaria drug development efforts because the pathway sits at the heart of several other biological processes currently being investigated as drug targets. So far, it is clear that the newly discovered pathway operates while the parasites are growing inside human blood cells. Next, the scientists will explore whether the parasite uses the same pathway during other stages of its lifecycle in humans and in mosquitoes, and how exactly it is involved in the metabolic control of the cell.

Immune evasion common in many viruses, bacteria and parasites is uncommon in M. tuberculosis

Mon, 24 May 2010 03:18:18 PDT

Scientists at NYU Langone Medical Center have discovered that the strategy of "immune evasion" common to many viruses, bacteria and parasites, is uncommon to M. tuberculosis where the antigens remain strikingly unchanged and homogenous. The study published in Nature Genetics on May 23, 2010, suggests that M. tuberculosis antigens do not mutate because they hope to be recognized by the body's immune system -- perhaps because the host immune mechanism that leads to the typical lung destruction and cough can contribute to the spread of the disease. This finding has the potential to change the direction of vaccine research and could result in a new focus on different targets of immune response to the bacteria. "The finding that the tuberculosis bacterium acts completely differently from other pathogens is quite surprising and unexpected," said Joel Ernst, MD, director of the division of Infectious Diseases and Immunology at NYU Langone Medical Center in NYC and lead author of the study. "If you get infected with the influenza virus, for example, the body's immune system recognizes it and tends to eliminate it. In tuberculosis, our immune response doesn't get rid of it -- it tends to hold on to it for a while -- keeping the bacteria under partial control."........> Full story

Easily blocked signaling protein may help scientists stop parasites

Thu, 20 May 2010 03:50:23 PDT

Researchers at Washington University School of Medicine in St. Louis have identified a parasite protein that has all the makings of a microbial glass jaw: it's essential, it's vulnerable and humans have nothing like it, meaning scientists can take pharmacological swings at it with minimal fear of collateral damage. The protein, calcium dependent protein kinase 1 (CDPK1), is made by Toxoplasma gondii, the toxoplasmosis parasite; cryptosporidium, which causes diarrhea; plasmodium, which causes malaria; and other similar parasites known as apicomplexans. In the May 20 issue of Nature, researchers report that genetically suppressing CDPK1 blocks the signals that toxoplasma parasites use to control their movement, preventing them from moving in and out of host cells. They also found that toxoplasma's version of CDPK1 is easier to disable than expected and identified a compound that effectively blocks its signaling ability. "Kinases are proteins that are common throughout biology, but the structures of CDPKs in apicomplexans much more closely resemble those found in plants than they do those of animals," says senior author L. David Sibley, PhD, professor of molecular microbiology. "We showed that these differences can be exploited to identify potent and specific inhibitors that may provide new interventions against disease."........> Full story

New twist on potential malaria drug target acts by trapping parasites in cells

Sat, 15 May 2010 04:13:31 PDT

Harvard School of Public Health (HSPH) researchers and colleagues seeking to block invasion of healthy red blood cells by malaria parasites have instead succeeded in locking the parasites within infected blood cells, potentially containing the disease.

The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world’s most common and dangerous infections.

Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.

Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.

After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.

“This is the stage where things have to happen very fast for the parasite,” said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. “The parasite doesn’t like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell.”........> Full story

Lake sturgeon have genes from parasite, signs of human STD

Wed, 12 May 2010 03:41:36 PDT

While trying to find a DNA-based test to determine the sex of lake sturgeon, Purdue University researchers found that the sturgeon genome contains trematode genes that didn't originally belong to it and may harbor a protozoan parasite that causes a sexually transmitted disease in humans.

Genetics professor Andrew DeWoody and postdoctoral associate Matthew C. Hale found the parasite and pathogen genes while analyzing DNA from the gonads of lake sturgeon, a species that is on the decline because of overfishing and pollution of its habitats. The only way to determine a lake sturgeon's sex currently is to examine its internal sexual organs.

DeWoody said about 15 genes found in the lake sturgeon came from Schistosoma, a parasitic worm. Lateral gene transfer from one organism to another is rare, especially in multicellular animals, he said, but could be part of some evolutionary process for the sturgeon. "Organisms may accept some new genes from other species because the new genes can serve as raw material for evolution," said DeWoody, whose findings were reported in the early online version of the journal Genetica. "The genome may be more fluid than we usually think."

Hale said genes often work in combination, and new genes may one day become involved with other genes to help the lake sturgeon create new traits needed to adapt to changes in its environment.

"It isn't necessarily a bad thing for the sturgeon. It probably doesn't have a cost," Hale said. "It's either neutral or has a benefit or it wouldn't be there.".......> Full story

Major breakthrough in the diagnosis of parasitic diseases

Wed, 28 Apr 2010 03:32:29 PDT

Chagas disease is one of the most deadly parasitic diseases in the world. It affects more than 10 million people, primarily in the Americas. In South America alone it kills 50 000 people each year. A reliable and rapid diagnosis is the key in the battle against infection but until now, this has been next to impossible. Dr. Momar Ndao and his team at the Research Institute of the MUHC have developed a new diagnostic approach that will help in the fight against Chagas disease.Their results were recently published in the Journal of Clinical Microbiology. Endemic in South America, the American trypanosomiasis, or Chagas disease, is transmitted to humans via the parasite Trypanosoma cruzi. The disease is usually transmitted through the bite of an infected insect or ‘kissing bug’. The symptoms are variable, but as the disease progresses serious chronic symptoms can appear, such as heart disease and malformation of the intestines. Most people affected may remain without symptoms for years, making diagnosis difficult. Chagas disease is also transmitted from mother to unborn child and can be passed on for as many as four generations without symptoms. "In other words, a person born in North America by a mother who was infected can transmit the disease to offspring without having traveled," says Dr. Ndao, Laboratory Director of the National Reference Center for Parasitology (NRCP) of the Research Institute. There is an urgent need for action on this disease as it is under-diagnosed and there is no effective treatment.......> Full story

Scientists Sever Molecular Signals That Prolific Parasite Uses to Puppeteer Cells

Sun, 25 Apr 2010 04:29:51 PDT

Scientists studying a cunning parasite that has commandeered the cells of almost half the world's human population have begun to zero in on the molecular signals that must be severed to free the organism's cellular hostages. While Toxoplasma gondii is not as widely known by the public as some of its more notorious parasitic brethren, it has been hijacking the cells of human and animal hosts for eons and is particularly dangerous to those with compromised and/or underdeveloped immune systems. "We have understood for some time now that Toxoplasma can co-opt the biological processes of its host cell, but there's still a lot we don't know about how this happens and what benefit the parasite derives," said Dr. Amos Orlofsky at Albert Einstein College of Medicine of Yeshiva University, one of the co-authors of a new paper in the Journal of Biological Chemistry that reveals how blocking certain signals within a cell can liberate it from its captor......> Full story

Scientists sever molecular signals that prolific parasite uses to puppeteer cells

Wed, 21 Apr 2010 04:05:00 PDT

Toward a 3-in-1 'dipstick' test for early detection of parasitic diseases

Mon, 22 Mar 2010 03:54:28 PDT

A new simple, inexpensive three-in-one test to diagnose a terrible trio of parasitic diseases that wreak havoc in the developing world is passing preliminary tests, scientists reported here today. Described during the 239th National Meeting of the American Chemical Society the test is for Chagas' disease, leishmaniasis, and "sleeping sickness" or African trypanosomiasis. This year will see about 800,000 new cases of Chagas disease, 2 million of leishmaniasis, and 70,000 of sleeping sickness (see sidebar). Most cases are discovered at a late stage, and together they cause tens of thousands of deaths each year and untold suffering. The drugs used to treat late-stage infections are often toxic and have potentially fatal side effects.......> Full story

Bt protein found effective against parasitic roundworm infections

Tue, 02 Mar 2010 03:51:42 PDT

Biologists at UC San Diego have discovered that a protein from a soil bacterium used to kill insects naturally on organic crops is a highly effective treatment for intestinal parasitic roundworms. These parasites, which include hookworms and whipworms, infect about two billion people in underdeveloped tropical regions and are cumulatively one of the leading causes of debilitation worldwide. The scientists report in the March 2 issue of the open-access journal PLoS Neglected Tropical Diseases, that a crystal protein known as Cry5B produced by the Bt, or Bacillus thuringiensis, bacterium is highly effective at a single dose at curing mammals of intestinal roundworm infections.......> Full story

NTU researchers complete the world's first in-depth study of the malaria parasite genome

Sat, 06 Feb 2010 03:37:07 PDT

Groundbreaking research done at Singapore's Nanyang Technological University's (NTU) School of Biological Sciences (SBS) could lead to the development of more potent drugs or a vaccine for malaria, which is transmitted to humans by infected mosquitoes and kills up to three million people each year. Assistant Professor Zbynek Bozdech and his team of researchers, including graduate students and post-doctorals from SBS' Division of Genomics & Genetics, have scored a world first in successfully using transcriptional profiling to uncover hitherto unknown gene expression (activity) patterns in malaria........> Full story

Parasitic wasps' newly sequenced genomes reveal new avenues for pest control

Sat, 16 Jan 2010 04:02:03 PDT

Researchers from the University of Geneva and the SIB Swiss Institute of Bioinformatics led an analysis of the sequenced genomes of parasitic wasps. Generally unknown to the public, the parasitic wasps kill pest insects. They are like 'smart bombs' that seek out and kill only specific kinds of insects. Harnessing their full potential would thus be vastly preferable to chemical pesticides, which broadly kill or poison many organisms in the environment, including humans. The results of this large study are featured in today's issue of Science. Professor Evgeny Zdobnov from the University of Geneva Medical School and the SIB Swiss Institute of Bioinformatics directed the comparative evolutionary genomics studies as part of this international project, which revealed many features that could be useful to pest control and medicine, and to enhance our understanding of genetics and evolution.......> Full story

Scientists hope to end sleeping sickness by making parasite that causes it self-destruct

Sat, 16 Jan 2010 03:56:20 PDT

After many years of study, a team of researchers is releasing data today that it hopes will lead to new drug therapies that will kill the family of parasites that causes a deadly trio of insect-borne diseases and has afflicted inhabitants of underdeveloped and developing nations for centuries. In an article to be published in today's issue of the Journal of Biological Chemistry, Vanderbilt University scientist Galina Lepesheva and her team are reporting their successful attempt at determining the structure of an enzyme essential to the survival of the protozoan parasites that cause sleeping sickness, Chagas disease and leishmaniasis. They say this new information provides the first up-close look at the busy enzyme and, perhaps more importantly, shows how one compound in particular prevents it from conducting business as usual.......> Full story

Sequencing wasp genome sheds new light on sexual parasite

Fri, 15 Jan 2010 04:41:56 PDT

About 100 million years ago, the bacterium Wolbachia came up with a trick that has made it one of the most successful parasites in the animal kingdom: It evolved the ability to manipulate the sex lives of its hosts. "When it developed this capability, Wolbachia spread rapidly among the world's populations of insects, mites, spiders and nematodes, producing the greatest pandemic in the history of life," says Seth Bordenstein, assistant professor of biological sciences at Vanderbilt, who is studying the relationship between this parasitic bacteria and Nasonia, a genus of small wasps that prey on various species of flies, including houseflies, blowflies and flesh flies.......> Full story

New Clues Into How Invasive Parasite Spreads

Mon, 07 Dec 2009 04:15:11 PDT

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a possible strategy against an invasive parasite that infects more than a quarter of the world's population, including 50 million Americans. The study, involving the single-celled parasite Toxoplasma gondii, was led by Amos Orlofsky, Ph.D., assistant professor of pathology at Einstein. The results, published in the current issue of the Journal of Immunology, suggest a new approach for treating toxoplasmosis, the disease caused by this parasite.......> Full story

Scientists Reveal Malaria Parasites' Tactics for Outwitting Our Immune Systems

Tue, 01 Dec 2009 04:10:51 PDT

Malaria parasites are able to disguise themselves to avoid the host's immune system, according to research funded by the Wellcome Trust and published today in the journal Proceedings of the National Academy of Sciences. Malaria is one of the world's biggest killers, responsible for over a million deaths every year, mainly in children and pregnant women in Africa and South-east Asia. It is caused by the malaria parasite, which is injected into the bloodstream from the salivary glands of infected mosquitoes. There are a number of different species of parasite, but the deadliest is the Plasmodium falciparum parasite, which accounts for 90 per cent of deaths from malaria.......> Full story

New Strategy To Find Drugs To Treat Neglected Parasitic Infection

Tue, 10 Nov 2009 06:45:00 PDT

Using an unconventional approach that they designed, University of Pittsburgh drug discoverers and their collaborators at Walter Reed Army Institute of Research have identified compounds that hold promise for treating leishmaniasis, a parasitic infection that many consider one of the world's most overlooked diseases. The findings are available online today in PLoS Neglected Tropical Diseases......> full story

New Insight in the Fight against the Leishmania Parasite

Mon, 26 Oct 2009 05:51:33 PDT

Professor Albert Descoteaux's team at Centre INRS – Institut Armand-Frappier has gained a better understanding of how the Leishmania donovani parasite manages to outsmart the human immune system and proliferate with impunity, causing visceral leishmaniasis, a chronic infection that is potentially fatal if left untreated. This scientific breakthrough was recently published in PLoS Pathogens.......> full story

Gilliam Fellow Finds a New Twist on How Some Parasites Move

Wed, 21 Oct 2009 05:48:21 PDT

In 1843, the Hungarian scientist David Gruby—considered the founder of medical microbiology—was studying a microscopic parasite in frog blood. The parasite seemed to propel itself forward like a corkscrew, so he named the creature Trypanosoma sanguinis, after the Greek word “trypanon,” or augur. The name stuck, and the term Trypanosome is now used to describe a genus of unicellular parasites that move in a similar way......> full story

Extreme Genetic Variability In Malaria Parasite Found

Fri, 16 Oct 2009 06:14:58 PDT

Researchers at the University of Maryland School of Medicine Center for Vaccine Development (CVD) have charted the extreme genetic differences that occur over time in the most dangerous malaria parasite in the world. While there is no approved vaccine for malaria, various experimental vaccines are in development. The CVD study suggests that developing a broadly protective vaccine for malaria may be challenging because the parasite's genetic makeup is so variable, constantly changing. If a vaccine targets only a single protein in the parasite, and there are many different versions of that protein......> full story

Caltech scientists get detailed glimpse of chemoreceptor architecture in bacterial cells

Fri, 25 Sep 2009 06:24:37 PDT

Using state-of-the-art electron microscopy techniques, a team led by researchers from Caltech has for the first time visualized and described the precise arrangement of chemoreceptors—the receptors that sense and respond to chemical stimuli—in bacteria. In addition, they have found that this specific architecture is the same throughout a wide variety of bacterial species, which means that this is a stable, universal structure that has been conserved over evolutionary time.......> full story

First Evolutionary Branching For Bilateral Animals Found

Fri, 25 Sep 2009 06:18:25 PDT

When it comes to understanding a critical junction in animal evolution, some short, simple flatworms have been a real thorn in scientists’ sides. Specialists have jousted over the proper taxonomic placement of a group of worms called Acoelomorpha. This collection of worms, which comprises roughly 350 species, is part of a much larger group called bilateral animals, organisms that have symmetrical body forms, including humans, insects and worms. The question about acoelomorpha, was: Where do they fit in?......> full story