Tuesday, September 30, 2008

Stomach Bug Appears To Protect Kids From Asthma

A long-time microbial inhabitant of the human stomach may protect children from developing asthma. Helicobacter pylori, a bacterium that has co-existed with humans for at least 50,000 years, may lead to peptic ulcers and stomach cancer. Yet, kids between the ages of 3 and 13 are nearly 59 percent less likely to have asthma if they carry the bug.

"Our findings suggest that absence of H. pylori may be one explanation for the increased risk of childhood asthma," says Yu Chen, Ph.D., assistant professor of epidemiology at New York University School of Medicine and a co-author of the study. "Among teens and children ages 3 to 19 years, carriers of H. pylori were 25 percent less likely to have asthma."


The impact was even more potent among children ages 3 to 13: they were 59 percent less likely to have asthma if they carried the bacterium, the researchers report. H. pylori carriers in teens and children were also 40 percent less likely to have hay fever and associated allergies such as eczema or rash.

Asthma has been rising steadily for the past half-century. Meanwhile H. pylori, once nearly universal in humans, has been slowly disappearing from developed countries over the past century due to increased antibiotic use, which kills off the bacteria, and cleaner water and homes, explains Dr. Blaser. Data from NHANES IV showed that only 5.4 percent of children born in the 1990s were positive for H. pylori, and that 11.3 percent of the participants under 10 had received an antibiotic in the month prior to the survey.

The rise in asthma over the past decades, Dr. Blaser says, could stem from the fact that a stomach harboring H. pylori has a different immunological status from one lacking the bug. When H. pylori is present, the stomach is lined with immune cells called regulatory T cells that control the body's response to invaders. Without these cells, a child can be more sensitive to allergens.

"Our hypothesis is that if you have Helicobacter you have a greater population of regulatory T-cells that are setting a higher threshold for sensitization," Dr. Blaser explains. "For example, if a child doesn't have Helicobacter and has contact with two or three cockroaches, he may get sensitized to them. But if Helicobacter is directing the immune response, then even if a child comes into contact with many cockroaches he may not get sensitized because his immune system is more tolerant."

In other words, the presence of the bacteria in the stomach may influence how a child's immune system develops: if a child does not encounter Helicobacter early on, the immune system may not learn how to regulate a response to allergens. Therefore, the child may be more likely to mount the kinds of inflammatory responses that trigger asthma.

"There's a growing body of data that says that early life use of antibiotics increases risk of asthma, and parents and doctors are using antibiotics like water," Dr. Blaser says. "The reality is that Helicobacter is disappearing extremely rapidly. In the NHANES IV study, less than six percent of U.S. children had Helicobacter, and probably two generations ago it was 70 percent. So, this is a huge change in human micro-ecology. The disappearance of an organism that's been in the stomach forever and is dominant is likely to have consequences. The consequences may be both good--less likelihood of gastric cancer and ulcers later in life--and bad: more asthma early in life."


Friday, September 26, 2008

New Species Of Bacteria Contaminates Hairspray

Scientists in Japan have discovered a new species of bacteria that can live in hairspray.

"Contamination of cosmetic products is rare but some products may be unable to suppress the growth of certain bacteria," says Dr Bakir from the Japan Collection of Microorganisms, Saitama, Japan. "We discovered a new species of bacteria called Microbacterium hatanonis, which we found contaminates hairspray."

"We also found a related species, Microbacterium oxydans in hairspray which was originally isolated from hospital material. Microbacterium species have been identified in milk, cheese, beef, eggs and even in the blood of patients with leukaemia, on catheters and in bone marrow."


The scientists looked at the appearance and diet of the bacterium, then analysed its genome to show that it is an entirely new species. "It has been named in honour of Dr Kazunori Hatano, for his contribution to the understanding of the genus Microbacterium," says Dr Bakir. Microbacterium hatanonis is rod-shaped and grows best at 30°C and pH neutral.

Scientists now need to determine the clinical importance of the new species, as similar bacteria have been found to infect humans. "Further testing will establish whether the species is a threat to human health," says Dr Bakir. "We hope our study will benefit the formulation of hairspray to prevent contamination in the future."

Source: ScienceDaily

Thursday, September 25, 2008

Tongue's sixth 'taste' discovered — calcium

Study finds new flavor mice can detect, suggesting people can as well

Here's the new taste sensation — your tongue might be able to taste calcium.

The capability to taste calcium has now been discovered in mice. With these rodents and humans sharing many of the same genes, the new finding suggests that people might also have such a taste. The four tastes we are most familiar with are sweet, sour, salty and bitter. Recently scientists have discovered tongue molecules called receptors that detect a fifth distinct taste — "umami," or savory.

"But why stop there?" asked researcher Michael Tordoff, a behavioral geneticist at the Monell Chemical Senses Center in Philadelphia. "My group has been investigating what we believe is another taste quality — calcium." So assuming the human palate can detect calcium, what does the mineral taste like?

"Calcium tastes calcium-y," Tordoff said. "There isn't a better word for it. It is bitter, perhaps even a little sour. But it's much more because there are actual receptors for calcium, not just bitter or sour compounds." One way we might regularly perceive calcium is when it comes to minute levels found in drinking water. "In tap water, it's fairly pleasant," Tordoff said. "But at levels much above that, the taste becomes increasingly bad."

There may be a strong link between the bitterness of certain vegetables and their calcium level. High-calcium vegetables include collard greens, bok choy,kale and bitter melon. One reason some people might avoid these veggies, Tordoff suggests, is because of their calcium taste.


Ironically, while milk and other dairy products are loaded with calcium, the mineral tends to bind to fats and proteins, which prevents you from tasting it in these foods.

Calcium important for survival
A taste receptor designed specifically for calcium
makes sense for our survival, since the mineral is key to cell biology and good bones. Low calcium intakes have been implicated in several chronic diseases in people, including osteoporosis, obesity and hypertension.

"Many animals have a specific calcium appetite, which implies they can detect the mineral and consume sufficient quantities of it to meet their needs," Tordoff said.

To investigate how this calcium appetite worked, Tordoff and his colleagues gave 40 different strains of mice a choice between water and a calcium solution to drink.

"Most mice dislike calcium, but we found a very unusual strain that drinks it avidly," Tordoff said. "The PWK strain drank about four times more calcium than water." By analyzing the DNA of this unusual strain, the researchers were able to identify two genes linked with consuming calcium.

One is a gene for a calcium-sensing receptor called CaSR, which has been found by other researchers in the kidney, brain and gut. "We didn't know it was on the tongue before," Tordoff said.

The other is a gene known as Tas1r3. This is a component of the "sweet-taste" receptor — a finding that researchers described as "very unexpected." By measuring the electrical activity of nerves linking the brain and tongue in mice, "we can now say with some certainty that calcium is tasted," Tordoff said.

While it remains to be seen if this discovery in mice also holds true for humans, "there are some tantalizing reports that suggest it does," Tordoff said. "We know people have the sweet-taste gene, Tas1r3, and the gene involved with the calcium-sensing receptor, CaSR. We don't know if we have the same forms of genes as the mice have, but it seems pretty likely they have the same function."

Confirming the existence of calcium taste receptors in people will require scientists to look at fresh human tongues. Tordoff said, tongue in cheek, that "hopefully we won't have to be sitting by as somebody dies to wait to chop their tongues off — we're not ambulance chasers. There are cases where people have cancer of the tongue and have to get them removed."

If calcium taste receptors are found in people, future research could then investigate whether it is possible to bypass these molecules, Tordoff told LiveScience. "People don't consume as much calcium as nutritionists would like, and one reason for this is that foods high in calcium don't taste good to many people," Tordoff said. "Tweaking its taste could encourage a calcium-deficient population to consume more of this key nutrient.


Thursday, September 18, 2008

Anthrax case spurs new germ-gene sleuthing

Microbial forensics may help exonerate or incriminate much like DNA can

The anthrax killer spurred a whole new branch of science that could give the United States a head start in the next emergency — whether it is investigating more bioterrorism or even a food poisoning outbreak. It is called microbial forensics, a way of using a germ's genetics to help exonerate or incriminate much as human DNA can today.

Microbes — whether bacteria like Salmonella and E. coli, or viruses like HIV — have unique genetic signatures that can allow scientists to tell even the most closely related strains apart. The forensics side comes from adding crime-investigation techniques to this advanced microbiology used by disease detectives.


With anthrax, that science led to a single flask of bacteria deemed the genetic parent of the spores grown for the 2001 attacks. It then took traditional gumshoe detective work for the FBI to finger the flask's owner, Dr. Bruce Ivins, as the alleged attacker while ruling out others who shared his Fort Detrick laboratory where that flask was stored.

If tracing a single vial of germs sounds impressive, consider: Research under way now might one day allow tracing where someone has recently traveled by the DNA of bacteria in the dirt on their shoes.But microbial forensics is a fledgling field, apparently used in court only once before — in the attempted-murder conviction of a doctor who injected a former lover with HIV taken from one of his patients.

The far more complicated anthrax case could prove pivotal in establishing the credibility of microbial forensics, even though Ivins' suicide means it won't go to court. Thus, scientists are clamoring to see the full evidence. The FBI has not yet released the actual genetic test results, although bits of the work have been published in scientific journals.

"Science is a wonderful thing but it is, at the end of the day, a tool," said Dr. Gigi Gronvall of the University of Pittsburgh's Center for Biosecurity. "The question is how that was used." Microbial forensics is "still a field very much in its infancy," said prominent gene researcher Dr. Claire Fraser-Liggett, whose former laboratory, the Institute for Human Genome Research, was tapped by the FBI to perform extensive anthrax testing. "There was always the lingering question as to whether you would ever really be able to find differences that would be useful in terms of doing attribution."

While the Federal Bureau of Investigation prohibited Fraser-Liggett from disclosing specifics, the investigation ultimately compared DNA from more than 1,000 anthrax samples, "finding that you could really apply many of the same parallels with human forensics to microbial forensics," she said.The implications, she added, "go very far beyond just this one case."

Unlike in 2001, today the genetic makeup of many bacteria and viruses has been fully sequenced, or decoded, and advanced machinery makes it possible to sequence more samples in a day or two, for under $1,000 each. So Fraser-Liggett urges development of a database of multiple samples of pathogens collected from around the world, so the next such investigation won't have to start from scratch.

"My recommendation would clearly be to not wait until something happens again, because it may not be with anthrax," she said. Bioterrorism aside, such testing could trace culprits in food poisonings and other outbreaks more precisely than today's more limited genetic fingerprinting, she added. But legally, microbial forensics raises enough issues that in 2004, the FBI created an elite committee of specialists in genetics and law enforcement to develop the first guidelines on how to handle and preserve bacteria or viruses that may be part of a crime.

In the anthrax case, simpler testing rapidly showed the attack bacteria was the so-called Ames strain, widely used in laboratory research. Summaries released by the FBI this week said fuller gene sequencing uncovered four specific mutations that gave the anthrax a unique signature. When compared to 1,000 Ames samples from 16 laboratories, only the germs in Ivins' flask matched. Scientists' top question: Were enough samples tested to be sure another source wasn't missed?

"Frankly, I have some level of skepticism," said Dr. Philip Russell, the U.S. Department of Health and Human Services emergency preparedness chief in 2001. He suggested an outside panel such as the National Academy of Sciences review the evidence. "They've got a heavy lift to convince the scientific world they've nailed it." Dr. Francis Collins, former genetics chief at the National Institutes of Health, wants to see complete sequences for each sample — from the first victim, the four letters, the flask, and the ruled-out supplies — and would check testing quality. Labs that repeat the sequencing multiple times can reduce the chance of error to one in a million or less, he said.

More information about the apparently unique mutations is a key, added Dr. Michael Stebbins, who directs the Federation of American Scientists' biosecurity project. Did they arise naturally when Ivins first grew his anthrax supply in 1997, or did he engineer them? "If they were engineered by Dr. Ivins, it's highly unlikely that they would pop up anywhere else," Stebbins said. "Their case hinges on the fact that these strains came out of this particular flask."


Monday, September 15, 2008

Cancer-inhibiting Compound Found Under The Sea

University of Florida College of Pharmacy researchers have discovered a marine compound off the coast of Key Largo that inhibits cancer cell growth in laboratory tests, a finding they hope will fuel the development of new drugs to better battle the disease.

The UF-patented compound, largazole, is derived from cyanobacteria that grow on coral reefs. Researchers, who described results from early studies today (Aug. 7) at an international natural products scientific meeting in Athens, Greece, say it is one of the most promising they've found since the college's marine natural products laboratory was established three years ago.


An initial set of papers in the Journal of the American Chemical Society also has garnered the attention of other scientists, and the lab is racing to complete additional research. The molecule's natural chemical structure and ability to inhibit cancer cell growth were first described in the journal in February and the laboratory synthesis and description of the molecular basis for its anticancer activity appeared July 2.

"It's exciting because we've found a compound in nature that may one day surpass a currently marketed drug or could become the structural template for rationally designed drugs with improved selectivity," said Hendrik Luesch, Ph.D., an assistant professor in UF's department of medicinal chemistry and the study's principal investigator.

Largazole, discovered and named by Luesch for its Florida location and structural features, seeks out a family of enzymes called histone deacetylase, or HDAC. Overactivity of certain HDACs has been associated with several cancers such as prostate and colon tumors, and inhibiting HDACs can activate tumor-suppressor genes that have been silenced in these cancers.

Although scientists have been probing the depths of the ocean for marine products since the early 1960s, many pharmaceutical companies lost interest before researchers could deliver useful compounds because natural products were considered too costly and time-consuming to research and develop.

Many common medications, from pain relievers to cholesterol-reducing statins, stem from natural products that grow on the earth, but there is literally an ocean of compounds yet to be discovered in our seas. Only 14 marine natural products developed are in clinical trials today, Luesch said, and one drug recently approved in Europe is the first-ever marine-derived anticancer agent.

"Marine study is in its infancy," said William Fenical, Ph.D., a distinguished professor of oceanography and pharmaceutical sciences at the University of California, San Diego. "The ocean is a genetically distinct environment and the single, most diverse source of new molecules to be discovered."

The history of pharmacy traces its roots back thousands of years to plants growing on Earth's continents, used by ancient civilizations for medicinal purposes, Fenical added. Yet only in the past 30 years have scientists begun to explore the organisms in Earth's oceans, he said. Fewer than 30 labs exist worldwide and research dollars have only become available in the past 15 years.

HDACs are already targeted by a drug approved for cutaneous T-cell lymphoma manufactured by the global pharmaceutical company Merck & Co. Inc. However, UF's compound does not inhibit all HDACs equally, meaning a largazole-based drug might result in improved therapies and fewer side effects, Luesch said.

Since 2006, Luesch and his team of researchers have screened cyanobacteria provided by collaborator Valerie Paul, Ph.D., head scientist at the Smithsonian Marine Station in Fort Pierce. They check the samples for toxic activity against cancer cells and last year encountered one exceptionally potent extract — the one that ultimately yielded largazole.

To conduct further biological testing on the compound, Luesch and his team have been collaborating with Jiyong Hong, an assistant professor in the department of chemistry at Duke University, to replicate its natural structure and its actions in the laboratory.

Luesch said that within the next few months he plans to study whether largazole reduces or prevents tumor growth in mice. Luesch has several other antitumor natural products from Atlantic and Pacific cyanobacteria in the pipeline.

"We have only scratched the surface of the chemical diversity in the ocean," Luesch said. "The opportunities for marine drug discovery are spectacular."

Source: ScienceDaily

Monday, September 8, 2008

Fungus Puts the Heat in Chili Peppers

There's a fungus among us chili fans—and some of the spicy peppers evolve their kick to repel it, a new study says.Chili peppers develop piquant chemicals to thwart the harmful microbes long enough to give birds and other animals a chance to disperse the pepper seeds, helping the chilies to procreate, scientists found.

Chilis high in chemicals called capsaicinoids occur most in areas where the fungus can enter the peppers through holes bored by insects, and these chilies are hotter, said study author Joshua Tewksbury, a biologist at the University of Washington in Seattle.


Gradient of Hotness

Tewksbury made the discovery after learning that some species of wild chilies in Bolivia have both pungent, spicy individuals and others that lack any kick whatsoever. "You can't tell them apart unless you chew on the fruits," he said.

Chewing on fruits—tough field work, Tewksbury joked—helped the team to establish a gradient of hotness along a 185-mile-long (300-kilometer-long) sample area in Bolivia. The northern end of the line is dominated by nonpungent chilies. The southern populations are much denser and hotter—really hot.

When the team examined fruits from along this transect, they found the pungent ones also had a greater concentration of scar damage from foraging insects similar to aphids and leaf hoppers. The skin on fruits, Tewksbury explained, is a first line of defense against microbes, which can't get past it on their own.

"Every time a bug pokes a hole in the chili fruit, the fungus can get in. And the more times the bugs can poke holes in the fruit, the more likely it is the fungus will start to invade," he said. Laboratory experiments showed capsaicinoids thwart the fungus invasion—but not the insects. "It looks like this chili is hot to stop the fungus, and the fungus is sort of mediated by these bugs," Tewksbury said.

Why Humans Eat Chilies

The finding, he said, adds weight to a hypothesis that humans first started to eat chilies for their antimicrobial properties. He noted that the majority of people who eat chilies live along the Equator, a region of the world where microbes also flourish and cause a range of intestinal diseases.

"We're simply co-opting the result of a very ancient evolutionary arms race between chilies and fungus and saying that will work for us too," he said.Linda Perry, an anthropologist at the Smithsonian Institution's National Museum of Natural History in Washington, D.C., said the new research clearly demonstrates that capsaicinoids evolved to thwart the fungus.

But the study does not show that capsaicinoids prevent foodborne illnesses or act as a preservative, said Perry, who is an expert on the domestication of chilies. Nor, she added, has it been demonstrated that the purported antimicrobial properties of chilies have much to do with their popularity. "I think people probably adopted chili peppers into their diet just because they taste good," she said.

Source: Nationalgeographic

Thursday, September 4, 2008

New Antibiotic Found in Fish Cells

Scientists have found that certain cells in a hybrid striped bass commonly available in the United States contain a new family of antibiotics. Edward Noga and Umaporn Silphaduang, both of North Carolina State University in Raleigh, have named the antibiotics "piscidins" for the Latin word for fish, pisces.

The piscidins are actually tiny protein antibiotics produced by mast cells, which are found in the immune systems of all vertebrates.


Many organisms produce their own antibiotics to protect themselves against disease-causing microbes. More than a decade ago, for example, researchers discovered that frogs oozed a new class of natural antibiotics in their skins, which were later named "magainins." Crocodiles produce unique antibiotics that circulate in their blood stream.

For years there has been considerable interest in discovering new antibiotics that can kill a variety of human pathogens. A growing number of bacteria are becoming resistant to existing antibiotics, and recent events such as the spread of anthrax and huge public demand for Cipro have given the search for new anti-microbial drugs greater urgency.

The mast cells in which the piscidins were found play a key role in allergic reactions. In people, mast cells release histamines and trigger reactions such as asthma and hay fever.

Although it's known that mast cells summon the immune system to respond when the body is threatened by invading bacteria, the discovery of antibiotics inside the fish mast cells is the first evidence that these cells may be able to kill bacteria directly, said Noga.

He is particularly excited about piscidins because he thinks it may be more difficult for bacteria to develop a resistance to this new class of antibiotics.

Many antibiotic drugs are designed to recognize a specific molecule on the outer surface of a bacterium, which then targets the microbe for destruction. But bacteria evolve very rapidly, and a single mutation that alters the look of the target molecule can help the bacterium evade annihilation.

The piscidins, however, mount a more general attack against some very common features of bacteria, says Noga, who is co-author of a report on the findings published in the journal Nature. "Piscidins make a hole in the membrane, which cause the bacteria to pop open and die within minutes," said Noga.

This general form of attack means that single mutations are unlikely to help bacteria evolve resistance. But despite the promising results, Noga remains cautious. "When it comes to nature, never say never," he said.

The finding may have significant implications not only for human medicine but also for veterinary medicine and the U.S. aquaculture industry

Source: Nationalgeographic