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Archive for February 28th, 2006

Dysentery Uses ‘Sword And Shield’ To Cause Infection

Posted by tumicrobiology on February 28, 2006

Source: Imperial College London

Scientists have found that the bacterium that causes dysentery uses a ‘sword and shield’ approach to cause infection.

According to research published today in Science, the team from Imperial College London and Institut Pasteur, Paris, found that shigella, the bacteria which causes dysentery, is able to invade cells, while stopping any response from the immune system.

They found that shigella was able to infect cells by using a secretion system to inject proteins into human cells, (the sword), while lipopolysaccharide (LPS) on the surface of the bacteria acts as a shield to protect the dysentery bacterium from being destroyed by the body’s immune system.

Dr Christoph Tang, from Imperial College London, and one of the researchers, comments: “This is the first description of bacteria able to use this ‘sword and shield’ approach, showing how dysentery is able to infect the body so effectively. We have shown why the bacteria can avoid being destroyed by the body’s immune responses through the expression of a molecule that acts as a shield on its surface.”

The researchers found that shigella, the bacteria causing dysentery uses a Type III secretion system to inject proteins into human cells. This causes the cells to become inflamed, resulting in symptoms of dysentery, such as bloody diarrhoea. At the same time, the LPS chains on the surface of the bacteria are shortened. This allows the needles to inject proteins, while protecting the bacteria from being destroyed by the immune system.

Dr Tang adds: “This discovery greatly expands our understanding of how bacteria are sometimes able to evolve although it is unlikely to result in new treatments or vaccines for dysentery. In this case, the dysentery bacteria has evolved into a highly effective and dangerous infection.”

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University Of Minnesota Scientists Engineer Radiation-Resistant Bacteria To Attack Pollutants

Posted by tumicrobiology on February 28, 2006

Bacteria that stand up to high-level radiation have been engineered to attack pollutants commonly found at radioactive waste sites. The bacteria, the product of work led by University of Minnesota biochemist Larry Wackett, could be further engineered to completely clean up organic solvents at waste sites. The work is published in the October issue of Nature Biotechnology.

The bacteria don’t naturally “eat” pollutants, but Wackett inserted genes that enabled the bacteria to attack–but not completely digest–solvents such as toluene and chlorobenzene, which are commonly used as carrier fluids for radioactive materials. Wackett said that with the addition of more genes, the bacteria may be engineered to completely digest the solvents, which can cause severe environmental damage. And there are plenty of solvents to digest: In the United States alone, approximately 3,000 nuclear waste sites still await cleanup.

The bacteria, named Deinococcus radiodurans, were discovered about 20 years ago in a can of irradiated meat, said Wackett.

“When exposed to radiation, the bacteria suffer chromosomal breakage and other damage,” he explained, “but they thrive because they have tremendous repair mechanisms.” In experiments conducted with colleagues Mike Daly and Ken Minton of the Uniformed Services University of the Health Sciences in Bethesda, Md., Wackett found that bacteria placed in a high-energy gamma-ray field were able to attack the pollutants with the same efficiency as did bacteria subjected to no radiation. Wackett said he and his colleagues are studying the genome of D. radiodurans to learn exactly how its metabolic machinery works. That information will be used to engineer the additional genes necessary to enable the organism to completely digest pollutants.

Source: University Of Minnesota

 

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MRSA Use Amoeba To Spread, New Research Shows

Posted by tumicrobiology on February 28, 2006

The MRSA ‘superbug’ evades many of the measures introduced to combat its spread by infecting a common single-celled organism found almost everywhere in hospital wards, according to new research published in the journal Environmental Microbiology.

Microscope image of an amoeba with epidemic MRSA stained green. (Image courtesy of University of Bath)Scientists from the University of Bath have shown that MRSA infects and replicates in a species of amoeba, called Acanthamoeba polyphaga, which is ubiquitous in the environment and can be found on inanimate objects such as vases, sinks and walls.

As amoeba produce cysts to help them spread, this could mean that MRSA maybe able to be ‘blown in the wind’ between different locations.

Further evidence from research on other pathogens suggests that by infecting amoeba first, MRSA may emerge more virulent and more resistant to antibiotics when it infects humans.

“Infection control policies for hospitals should recognise the role played by amoeba in the survival of MRSA, and evaluate control procedures accordingly,” said Professor Mike Brown from the Department of Pharmacy and Pharmacology at the University of Bath.

“Until now this source of MRSA has been totally unrecognised. This is a non-patient source of replication and given that amoeba and other protozoa are ubiquitous, including in hospitals, they are likely to contribute to the persistence of MRSA in the hospital environment”.

“Adding to the concern is that amoebal cysts have been shown to trap pathogens and could potentially be dispersed widely by air currents, especially when they are dry.

“Replication of MRSA in amoeba and other protozoa raises several important concerns for hospital hygiene.”

In laboratory tests, the researchers found that within 24 hours of its introduction, MRSA had infected around 50 per cent of the amoeba in the sample, with 2 per cent heavily infected throughout their cellular content.

Evidence with other pathogens suggests that pathogens that emerge from amoeba are more resistant to antibiotics and more virulent.

“This makes matters even more worrying,” said Professor Brown.

“It is almost as though the amoeba act like a gymnasium; helping MRSA get fitter and become more pathogenic.

“In many ways this may reflect how this kind of pathogenic behaviour first evolved. A good example is the bacterium that causes legionnaires disease. Probably it was pathogenic long before humans and other animals arrived on the evolutionary scene. Even today, it has no known animal host.

“The most likely reason is that Legionella and many pathogens learned their pathogenicity after sparring with single-celled organisms like amoeba for millions of years. Because our human cells are very similar to these primitive, single-celled organisms, they have acquired the skills to attack us”.

For these reasons, such primitive cells are being used to replace animals for many kinds of biological tests.

“Effective control of MRSA within healthcare environments requires better understanding of their ecology,” said Professor Brown.

“We now need to focus on improving our understanding of exactly how MRSA is transmitted, both in hospitals and in the wider environment, to develop control procedures that are effective in all scenarios.”

Recently released figures show that infections caused by MRSA rose 5 per cent between 2003 and 2004, and mortality rates increased 15-fold between 1993 and 2002.

The research paper has been published online (see link) and will appear in the June or July print issue of Environmental Microbiology which will be published mid-May or mid-June respectively.

The work was funded by The Lord Dowding Fund for Humane Research and also the UK Department of Health.

Source: University of Bath

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A Case Of Mistaken Molecular Identity

Posted by tumicrobiology on February 28, 2006

Researchers in Argentina have determined that night blindness is a new clinical symptom of Chagas disease. A team led by Howard Hughes Medical Institute (HHMI) international research scholar Mariano Jorge Levin and Cristina Paveto of the Institute for Genetic Engineering and Molecular Biology (INGEBI), National Research Council, National Council of Scientific Research and Technology in Buenos Aires, found that the immune system of individuals with the tropical disease can shut down a key reaction in the retina, causing night blindness.
Triatomine bug, Trypanosoma cruzi vector, defecating on the wound after taking a blood meal. (Image courtesy of DPDx Parasite Image Library / Centers for Disease Control and Prevention)”This is a new observation, a new clinical symptom of Chagas disease,” said Levin, head of the Laboratory of the Molecular Biology of Chagas Disease at the University of Buenos Aires, Argentina. Levin and colleagues report their findings in the March 2006, issue of the FASEB Journal.

Chagas disease affects people living in regions of Latin America where insects carrying the parasite Trypanosoma cruzi thrive in crowded and substandard housing. At night, the insects emerge and bite, transferring the Chagas parasite into a new host. Their victims are often children. After an acute infection characterized by swollen eyelids, those infected usually feel better. But the parasite remains active inside them, in a chronic phase of infection, quietly invading cells and stimulating the immune system. As a result, people can develop heart and gastrointestinal problems months or years after being infected. Some 30,000 people die each year from Chagas disease, according to the World Health Organization, but the number of people who are carrying latent infections is unknown.

“We now know that Chagas patients may have trouble seeing at night,” said Levin. “And this gives us additional motivation to improve conditions for people living in areas where Chagas disease is common.”

Silvia Matsumoto, a physician from the Dr. Teodoro Alvarez Hospital in Buenos Aires and first author of the paper, launched the investigation after noticing Chagas patients complaining about vision problems. “This was her idea, that the same antibodies that touch the heart cells might also block rhodopsin,” said Levin.

Matsumoto conducted thorough eye examinations of 45 Chagas disease patients with heart problems. She found that under bright conditions, the Chagas patients performed comparably to 50 healthy control individuals. But in the dark, 37 of 45 (82 percent) Chagas patients had trouble seeing with at least one eye, and 19 of 45 (42 percent) had trouble with both eyes. Matsumoto then approached Paveto, and both contacted Levin, whose laboratory was well-stocked with antibodies from Chagas patients and who had already developed the tests needed to study molecular mimicry.

In previous research, Levin and colleagues showed that the immune systems of patients infected by T. cruzi generate antibodies that attack the parasite but also cause damage to heart cells. Levin suspected “molecular mimicry” as the cause of the misguided attack. Molecular mimicry occurs when a molecule that is part of an infectious agent resembles a molecule native to the body. Eventually, the immune system begins to mistake the native molecule for the invader. Levin’s investigations revealed that an intra-cellular T. cruzi protein resembles the beta1-adrenergic receptor on the surface of heart cells, a finding that helped explain why Chagas patients develop certain heart problems.

Now, it turns out, molecular mimicry can also upset the delicate machinery inside retinal cells. Levin and his team found that antibodies geared to attack T. cruzi also block rhodopsin, a molecule that converts light into electrical impulses sent to the brain. “Rhodopsin takes light and transforms it — that’s its function,” said Levin.

To demonstrate molecular mimicry in the retina, Paveto extracted rhodopsin from cow’s eyes. Through a series of tests, the team showed that cow rhodopsin, which is similar to the human protein, reacts with antibodies produced by Chagas patients.

“We showed that the same antibodies that attack heart cells can also interfere with rhodopsin,” Levin said. “This is important, because it enlarges the concept of molecular mimicry in Chagas disease.” Rhodopsin and beta1-adrenergic receptors in heart cells belong to the same class of molecules, a subfamily of the G-protein-coupled receptors, he pointed out.

Paveto, an independent researcher at INGEBI–an institute that is home to three HHMI international research scholars–conducted much of the painstaking work on the project by developing an original method to test rhodopsin function, said Levin.

Levin said that Chagas patients’ vision problems are caused exclusively by the antibodies that block rhodopsin, and not by inflammation. “In the hearts of Chagas patients, we see scarring because there is a complex reaction that causes inflammation,” he said. “But there are no such scars in the eyes of Chagas patients with reduced vision.”

“No one knew about the night blindness, so we don’t know, for instance, if Chagas patients have more accidents at night,” Levin added. “That’s one of many ideas to explore now. The research also points out that we need new drugs or vaccines to stop the parasite, and at a social level, it stresses the need to improve living conditions of Chagas patients, particularly those living in rural areas.”

Source: Howard Hughes Medical Institute

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