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Mechanism of Zeta Toxin Bacterial Suicide Explained

The zeta toxins are a family of proteins that are normally present within various pathogenic bacteria and can mysteriously trigger suicide when the cells undergo stress. A team led by Dr. Anton Meinhart at the Max Planck Institute for Medical Research in Heidelberg has now found the mechanism underlying this programmed bacterial cell death. The team’s paper, published in PLoS Biology, reports that zeta toxins convert a compound required for bacterial cell wall synthesis into a poison that kills bacteria from within. In the future, it may be possible to hijack this mechanism for defense against bacteria and to design drugs that mimic these toxins. Most bacteria harbor toxin-antitoxin (TA) systems, in which a bacterial toxin lies dormant under normal conditions, prevented from being active by its antitoxin counterpart. As long as the antitoxin is present, the bacterium can continue to exist and is not affected by the TA system. Under conditions of stress, however, the antitoxin is degraded, freeing the toxin to attack its host from within. Although the family of zeta toxins was discovered almost 20 years ago, their deadly mechanism has been enigmatic until now. The first author on the paper, Dr. Hannes Mutschler, and his colleagues studied the molecular mechanism of action of the zeta toxin PezT from the PezAT (Pneumococcal epsilon zeta Antitoxin Toxin) system using the model bacterium Escherichia coli. The PezAT system is found in the major human pathogen Streptococcus pneumoniae - a bacterium that causes serious infections such as pneumonia, septicemia, and meningitis. Bacterial cells in which PezT was activated showed symptoms of poisoning similar to the effects of penicillin. This involved first stalling in the middle of their division stage, and later the intersection zone between the two cell bodies burst and the cells died.

Complement-Regulating Genes Implicated in Preeclampsia

Scientists have discovered genetic defects that appear to predispose women to a common pregnancy-related medical problem called preeclampsia that can threaten the life of both baby and mother. Lead investigator Dr. Jane Salmon, a rheumatologist and senior scientist at the Hospital for Special Surgery in New York City, and colleagues uncovered genetic mutations in women with certain autoimmune diseases associated with increased risk of preeclampsia, as well as in patients with preeclampsia who did not have an autoimmune disease. Their findings appear in an article published online on March 22, 2011, in PLoS Medicine. Preeclampsia affects up to 10 percent of pregnancies in the United States. The condition claims the lives of more than 60,000 women each year in developing countries. It is diagnosed by the onset of high blood pressure and appearance of protein in the urine. Because the cause of preeclampsia is unknown, there are no reliable means to predict its occurrence and no satisfactory prevention or treatment. When preeclampsia becomes life-threatening, the only option is to deliver the baby pre-term. In the study, Dr. Salmon and colleagues focused on women with systemic lupus erythematosus and/or antiphospholipid antibody syndrome, which are autoimmune diseases. The women are participants in a multi-center research initiative led by Dr. Salmon known as PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) and funded by the National Institutes of Health since 2003 to identify biomarkers that predict poor pregnancy outcomes in women with lupus and/or antiphospholipid antibody syndrome. Dr. Salmon is also co-director of the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery.

Newly Discovered Bunya Virus Implicated in Deadly Chinese Outbreaks

Five years ago, large numbers of farmers in central China began falling victim to a mysterious disease marked by high fever, gastrointestinal disorder, and an appalling mortality rate — as high as 30 percent in initial reports. Investigators from the Chinese Center for Disease Control and Prevention hurried to the scene of the outbreak. On the basis of DNA evidence, they quickly concluded that it had been caused by human granulocytic anaplasmosis (HGA) bacteria, which are transmitted by tick bites. Now, however, subsequent studies have shown that this original conclusion was incorrect, and that a previously unknown and dangerous virus has been responsible for seasonal outbreaks of the disease in six of China's most populated provinces. "We expected to find a bacterial infection behaving in an unexpected way — human anaplasmosis has a less than one percent fatality rate in the U.S., and it rarely causes abdominal pain or vomiting or diarrhea," said Dr. Xue-Jie Yu of the University of Texas Medical Branch at Galveston, lead author of a paper on the discovery published online on March 16, 2011, in the New England Journal of Medicine. "Instead, we found an unknown virus." Researchers have named the newly discovered pathogen Severe Fever with Thrombocytopenia Syndrome virus (SFTSV), and placed it in the Bunyaviridae family, along with the hantaviruses and Rift Valley Fever virus. Later investigation has placed its mortality rate at 12 percent, still alarmingly high. Dr. Yu, a specialist in tick-borne bacteria like the species responsible for HGA, first suspected that a virus might be responsible for the outbreaks after close examination of patients' clinical data showed big differences from symptoms produced by HGA, and blood sera drawn from patients revealed no HGA bacteria or HGA antibodies. Dr.

First Partial Sequencing of an Iberian Pig, Prized for Its Meat

Researchers of the Faculty of Veterinary Medicine at Universitat Autònoma de Barcelona (UAB) and of the Centre for Research in Agricultural Genomics (CRAG), the Centre for Genomic Regulation (CRG) in Barcelona, the National Institute for Agrarian Technology and Research in Madrid and Wageningen Research Center (WUR, the Netherlands) have published the first partial genome sequencing of an Iberian pig. Using next-generation sequencing techniques, researchers have been able to sequence and analyze 1% of the genome. This is the first time an individual pig genome-sequence has been published. The project, coordinated by ICREA researcher Miguel Pérez-Enciso, was published online on March 16, 2011, in the journal Heredity. The sequenced animal is an Iberian sow from the Guadyerbas strain, a highly particular line which has been kept isolated on an experimental farm belonging to the government of Castilla-La Mancha and located in Oropesa, near Toledo, since 1945, thanks to years of work by INIA researchers. The Guadyerbas line thus represents one of the first original strains of the Iberian pig in Spain. These animals have a good appetite, are slow-growing, obese, hairless and black-colored. UAB and INIA teams have used these animals in several experiments aimed at identifying the genetic basis of the highly reputed meat quality of Iberian pigs. Researchers expect therefore that a complete sequencing could offer clues to these and other characteristics. The sequenced animal is highly inbred, because the herd has been isolated for over 50 years. Researchers have taken this into account with the intention of using a particularly 'homogeneous' species presenting little variability. Nevertheless, data from the sequencing offers surprising results, such as a higher than expected level of variability.

Bacterial Enzyme Inhibits Formation of Dental Plaque

Investigators from Japan show in vitro that the bacterium Streptococcus salivarius, a non-biofilm forming, and otherwise harmless inhabitant of the human mouth, actually inhibits the formation of dental biofilms, otherwise known as plaque. Two enzymes this bacteria produces are responsible for this inhibition. The research is published in the March 1, 2011 issue of the journal Applied and Environmental Microbiology. "FruA may be useful for prevention of dental caries," corresponding author Dr. Hidenobu Senpuku, of the National Institute of Infectious Diseases, Tokyo, said of one of the enzymes. "The activity of the inhibitors was elevated in the presence of sucrose, and the inhibitory effects were dependent on the sucrose concentration in the biofilm formation assay medium," the researchers wrote. "We show that FruA produced by S. salivarius inhibited S. mutans biofilm formation completely in the in vitro assay supplemented with sucrose," the researchers wrote. S. salivarius is the primary species of bacteria inhabiting the mouth, according to the report. The authors suggest that FruA may actually regulate microbial pathogenicity in the oral cavity. They found that a commercial FruA, produced by Aspergillus niger, was as effective as S. salivarius FruA at inhibiting S. mutans biofilm formation, despite the fact that its amino acid composition is somewhat different from that of S. salivarius. FruA is produced not only by S. salivarius, but by other oral streptococci. Much of the oral microbial flora consists of many beneficial species of bacteria that help maintain oral health and control the progression of oral disease. [Press release] [AEM abstract]

Cell Studies Yield Breakthrough in Niemann-Pick Type C Research

A paper announcing a breakthrough discovery in the fight against Niemann-Pick Type C (NPC), co-authored by Drs. Olaf Wiest and Paul Helquist of the University of Notre Dame's Department Chemistry & Biochemistry and Dr. Frederick Maxfield, Chair of Biochemistry at Cornell University Weill College of Medicine, was published online on March 21, 2011, in PNAS. The reported research shows, in cell culture, how use of a histone deacetylase inhibitor corrects the damage done by the genetic disorder and allows once-diseased cells to function normally. NPC involves a genetic flaw that keeps cells from using lipids appropriately and leaves the lipids trapped in the cell. Brain cells are especially impacted, and destruction of brain cells typically kills victims by their teen years and there is currently no treatment available in the U.S. NPC is an inherited cholesterol metabolism disorder that strikes one in every 150,000 children. It has been referred to by the National Institutes of Health as "childhood Alzheimer's" because of similarities in the brains of NPC and Alzheimer's disease patients. Three of the four grandchildren of former Notre Dame head football coach Ara Parseghian died of NPC, and the University has been involved in research on the disorder for years. Last year, it formally united with the Parseghian Foundation, which sponsored this work. Last summer, Notre Dame College of Science Dean Gregory Crawford and his wife Renate bicycled 2,300 miles from Tucson to Notre Dame to raise awareness of the newly strengthened partnership with the Parseghian Foundation. Notre Dame's Center for Rare and Neglected Diseases works to develop therapies and outreach efforts for people suffering from rare conditions, like NPC, that have been largely ignored by pharmaceutical companies. A team of researchers led by Drs.

New Beetle Species Named for Teddy Roosevelt

A new species of a rugged darkling beetle that thrives in an arid region of the Chihuahuan Desert is being named in honor of Theodore Roosevelt on the 100th anniversary of a speech he gave at Tempe Normal School, now Arizona State University (ASU). The speech, delivered March 20, 1911, focused on the role of government, the importance of an educated citizenry, and the "far-sighted wisdom" of the Territory of Arizona. The new species of beetle, Stenomorpha roosevelti, covered in thick dark hair with golden setal pads on tarsal segments of legs, was discovered in the protected area of Cuatro Ciénegas, a biodiversity-rich oasis in Coahuila, Mexico. It was discovered and named by Dr. Aaron Smith, an authority on darkling beetles and a postdoctoral research associate at ASU; Dr. Kelly Miller, an assistant professor and curator of arthropods for the Museum of Southwestern Biology at the University of New Mexico; and Dr. Quentin Wheeler, a professor and founding director of the International Institute for Species Exploration at ASU. "We wanted to do something distinct and long lasting to mark Roosevelt's impact on Arizona and conservation as we ramp up to the state centennial next year," said Dr. Wheeler, an ASU vice president and dean of the College of Liberal Arts and Sciences. According to Douglas Brinkley's book, "The Wilderness Warrior: Theodore Roosevelt and the Crusade for America," it was Roosevelt's executive orders that saved such natural treasures as Devils Tower, the Petrified Forest, and Arizona's Grand Canyon. "Naming a new species for President Roosevelt honors his achievements as a pioneering conservationist, naturalist and explorer, and helps us bring attention to biodiversity and the field of taxonomy. The ruggedness of this darkling beetle reflects many of the hardy and resilient characteristics of President Roosevelt," said Dr.

Exotic Kingfisher on Verge of Extinction

The Tuamotu kingfisher is a multicolored, tropical bird with bright blue feathers, a dusty orange head, and a bright green back. The entire population of these birds – fewer than 125 – lives on one tiny island in the south Pacific, and without serious intervention, they will soon no longer exist. One University of Missouri researcher is trying to stop the birds' extinction by working with farmers and residents on the island inhabited by the kingfishers. "If we lose these birds, we lose 50,000 years of uniqueness and evolution," said Dr. Dylan Kesler, assistant professor in fisheries and wildlife at the University of Missouri's School of Natural Resources in the College of Agriculture, Food and Natural Resources. "Because it has lived in isolation for a very long time, it's unlike any other bird. There is no other bird like this on the planet." In new studies published in the journal The Auk (published by the American Ornithologists Union) and the Journal of Wildlife Management, Dr. Kesler and his team of researchers have uncovered important information to help ensure the birds' survival and a unique way to attach radio transmitters to the birds to track them. To survive, the kingfishers need several specific habitat characteristics: (1) Hunting Perches about 5 feet off the ground – The birds hunt by "pouncing." They watch their prey and then fall on them from hunting perches about 5 feet high. Without the perches in broadleaf trees at the appropriate height, the birds have no way to hunt. (2) Exposed ground – the birds' food consists mainly of lizards, which are easier to spot where the ground is clear of vegetation. When coconut farmers conduct intermediate burns on their land – which are hot enough to kill brush, but do not lead to widespread fires or kill the lizards – it exposes more ground and the birds can see the lizards.

Jumping Gene Used in New Method to Study Gene Regulation

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have developed a new method for studying gene regulation, by employing a jumping gene as an informant. Described online on March 21, 2011, in Nature Genetics, the new method is called GROMIT. It enables researchers to systematically explore the very large part of our genome that does not code for proteins, and which likely plays a large role in making each of us unique, by controlling when, where, and to what extent genes are expressed. Thanks to GROMIT, scientists can also create mouse models for human diseases such as Down syndrome. "Our findings change how we think about gene regulation, and about how differences between individual genomes could lead to disease," said Dr. François Spitz from EMBL, who led the study. Until now, scientists thought that regulatory elements essentially controlled a specific gene or group of genes. With GROMIT, Spitz and colleagues discovered that the genome is not organized in such a gene-centric manner. Instead, it appears that each regulatory element can potentially control whatever is within its reach. This means that mutations that simply shuffle genetic elements around (without deleting or altering them) can have striking effects, by bringing genes into or out of specific regulators' zones of influence. The EMBL scientists also discovered that many of these regulatory elements act in specific tissues, which suggests that the expression levels of every gene, even those that are active all over the body, are fine-tuned at the tissue level. Jumping genes – or transposons – are sequences of DNA that can move from place to place within a cell's genome. This can have detrimental effects, for example if this extra genetic material is inserted into an important gene, disrupting it. But Dr.

LincRNA Plays Key Role in Determining Cell Identity

If some of your brain cells suddenly decided to become fat cells, it could cloud your decision-making capacity. Fortunately, early in an organism's development, cells make firm and more-or-less permanent decisions about whether they will live their lives as, say, skin cells, brain cells, or fat cells. These decisions essentially boil down to which proteins, among all the possible candidates encoded in a cell's genes, the cell will tend to make under ordinary circumstances. But exactly how a cell chooses its default protein selections from an overwhelmingly diverse genetic menu is somewhat mysterious. A new study from the Stanford University School of Medicine and collaborating institutions may help solve the mystery. The researchers discovered how a particular variety of the biomolecule RNA that had been thought to be largely irrelevant to cellular processes plays a dynamic regulatory role in protein selection. In unraveling this molecular mechanism, the study also offers enticing clues as to how certain cancers may arise. Dr. Howard Chang, associate professor of dermatology at Stanford, is the senior author of the study, published online on March 20, 2011, in Nature. "All the cells in your body have the same genes, but they don't all make the same proteins," said Dr. Chang, who is also a Howard Hughes Medical Institute Early Career Scientist. In this new study, Dr. Chang and his colleagues identified a novel action by a subset of RNA that reinforces cells' decisions about which combinations of their genes are to be active and which must stay silent. RNA, according to older textbooks, mainly functions as a messenger: a copy of a gene, made by a cell's gene-reading machinery, that can float away from the chromosomes where genes reside to other places in the cell where proteins are made.

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