THE RELATIONSHIP OF THE "MICROBIOME" AND INFECTIOUS DISEASE OUTBREAKS

FROM:  THE NATIONAL SCIENCE FOUNDATION 

"Microbiome" of Sierra Nevada yellow-legged frogs shifts during infectious disease outbreaks

Interaction between microbiome and infectious pathogens may drive disease
The adult human body is made up of some 37 trillion cells. But microbes, mainly bacteria, outnumber our body's cells by a ratio of 10-to-1.

Scientists now recognize that this huge community of benign microbes--called the microbiome--affects the health, development and evolution of all multicellular organisms, including humans.

Studies show that interactions between such microbiomes and pathogens, or disease-causing microorganisms, can have profound effects on infectious diseases.

In results of a new study, scientists from the University of California, Santa Barbara (UCSB) demonstrate that a fungal pathogen of amphibians does just that. The findings appear this week in the journal Proceedings of the National Academy of Sciences.

Infectious pathogens may disrupt the microbiome

Experiments with model organisms such as mice have shown that infectious pathogens can disrupt the microbiome, but the extent to which this process shapes disease outbreaks is largely unknown.

The work, conducted by scientists Cherie Briggs and Andrea Jani of UCSB, addresses a gap in disease ecology and microbiome research.

"This study shows the importance of knowing how the many benign microbes living on and in our bodies interact with those that cause disease," says Sam Scheiner, National Science Foundation program director for the joint NSF-NIH-USDA Ecology and Evolution of Infectious Disease Program, which funded the research.

"The results are important for developing responses to a disease that's causing amphibians to go extinct worldwide," says Scheiner, "and have implications for future studies of human health."

Jani and Briggs found that the fungus Batrachochytrium dendrobatidis (Bd) drives changes in the frogs' skin microbiomes during disease outbreaks in four populations of the Sierra Nevada yellow-legged frog (Rana sierrae).

Chytridiomycosis, an infectious disease of amphibian skin caused by the Bd pathogen, is a leading cause of amphibian losses worldwide.

"Since amphibian skin is the organ infected by Bd, there has been a lot of interest in how anti-fungal properties of some skin bacteria may protect the frogs," says Briggs.

"We focused on the flip side of this interaction: how infection with Bd can disrupt the skin microbial community."

Next-generation DNA sequencing documents changes

"We used next-generation DNA sequencing to document shifts in skin bacteria communities of the frogs during Bd outbreaks," Jani says.

"We paired field surveys with laboratory infection experiments, demonstrating a causal relationship in which Bd altered the frog's microbiome."

The researchers found that the severity of infection with Bd is strongly correlated with the composition of bacteria communities on the frogs' skin.

"It was surprising that across the different frog populations, there was a striking consistency in the correlation with Bd," says Jani.

One of the populations crashed due to Bd infection, but the other three populations tolerated Bd infections.

"There are different disease dynamics going on," says Jani, "yet there's a similar relationship between the microbiome and Bd."

Answers still elusive

The researchers were unable to conclusively determine whether the Bd-induced disturbance of the frog skin microbiome contributed to the disease symptoms.

The pathogens may interact with the microbiome directly or by manipulating the frogs' immune systems.

It's possible, the biologists say, that the pathogens directly compete with certain bacteria for space or resources or release compounds that affect some bacteria species.

Or the pathogens may control frog immune responses to favor their own growth and disrupt the normal microbiome.

The researchers say that promise exists for probiotic treatments as a way of fighting the decline of frogs due to Bd, but they're careful to qualify the statement.

There is a lot they still don't understand about the environmental effects of such treatments or the interactions between the frogs' microbiomes and the Bd pathogen.

-- Cheryl Dybas, NSF
-- Julie Cohen, UCSB (
Related Programs
Ecology of infectious disease

CLAYS STUDIED FOR SUPERBUG KILLING PROPERTIES

 FROM:  NATIONAL SCIENCE FOUNDATION 

New answer to MRSA, other 'superbug' infections: clay minerals?

Researchers discover natural clay deposits with antibacterial properties

Superbugs, they're called: Pathogens, or disease-causing microorganisms, resistant to multiple antibiotics.

Such antibiotic resistance is now a major public health concern.

"This serious threat is no longer a prediction for the future," states a 2014 World Health Organization report, "it's happening right now in every region of the world and has the potential to affect anyone, of any age, in any country."

Could the answer to this threat be hidden in clays formed in minerals deep in the Earth?

Biomedicine meets geochemistry

"As antibiotic-resistant bacterial strains emerge and pose increasing health risks," says Lynda Williams, a biogeochemist at Arizona State University (ASU), "new antibacterial agents are urgently needed."

To find answers, Williams and colleague Keith Morrison of ASU set out to identify naturally-occurring antibacterial clays effective at killing antibiotic-resistant bacteria.

The scientists headed to the field--the rock field. In a volcanic deposit near Crater Lake, Oregon, they hit pay dirt.

Back in the lab, the researchers incubated the pathogens Escherichia coli and Staphylococcus epidermidis, which breeds skin infections, with clays from different zones of the Oregon deposit.

They found that the clays' rapid uptake of iron impaired bacterial metabolism. Cells were flooded with excess iron, which overwhelmed iron storage proteins and killed the bacteria.

"The ability of antibacterial clays to buffer pH also appears key to their healing potential and viability as alternatives to conventional antibiotics," state the scientists in a paper recently published in the journal Environmental Geochemistry and Health.

"Minerals have long had a role in non-traditional medicine," says Enriqueta Barrera, a program director in the National Science Foundation's (NSF) Division of Earth Sciences, which funded the research.

"Yet there is often no understanding of the reaction between the minerals and the human body or agents that cause illness. This research explains the mechanism by which clay minerals interfere with the functioning of pathogenic bacteria. The results have the potential to lead to the wide use of clays in the pharmaceutical industry."

Ancient remedies new again

Clay minerals, says Williams, have been sought for medicinal purposes for millennia.

Studies of French clays--green clays historically used in France in mineral baths--show that the clays have antibacterial properties. French green clays have been used to treat Mycobacterium ulcerans, the pathogen that causes Buruli ulcers.

Common in Africa, Buruli ulcers start as painful skin swellings. Then infection leads to the destruction of skin and large, open ulcers on arms or legs.

Delayed treatment--or treatment that doesn't work--may cause irreversible deformities, restriction of joint movement, widespread skin lesions, and sometimes life-threatening secondary infections.

Treatment with daily applications of green clay poultices healed the infections. "These clays," says Williams, "demonstrated a unique ability to kill bacteria while promoting skin cell growth."

Unfortunately, the original French green clays were depleted. Later testing of newer samples didn't show the same results.

Research on French green clays, however, spurred testing of other clays with likely antibacterial properties.

"To date," says Williams, "the most effective antibacterial clays are those from the Oregon deposit."

Samples from an area mined by Oregon Mineral Technologies (OMT) proved active against a broad spectrum of bacteria, including methicillin-resistant S. aureus (MRSA) and extended-spectrum beta-lactamase-resistant E. coli (ESBL).

What's in those rocks?

Understanding the geologic environment that produces antibacterial minerals is important for identifying other promising locations, says Williams, "and for evaluating specific deposits with bactericidal activity."

The OMT deposit was formed near volcanoes active over tens to hundreds of thousands of years. The Crater Lake region is blanketed with ash deposits from such volcanoes.

OMT clays may be 20 to 30 million years old. They were "born" eons before deposits from volcanoes such as Mt. Mazama, which erupted 7,700 years ago to form the Crater Lake caldera.

Volcanic eruptions over the past 70,000 or so years produced silica-rich magmas and hydrothermal waters that may have contributed to the Oregon deposit's antibacterial properties.

To find out, Williams and Morrison took samples from the main OMT open pit. Four types of rocks were collected: two blue clays, and one white and one red "alteration zone" rock from the upper part of the deposit.

Blue clay to the rescue

The OMT blue samples were strongly bactericidal against E. coli and S. epidermidis. The OMT white sample reduced the population of E. coli and S. epidermidis by 56 percent and 29 percent, respectively, but the red sample didn't show an antibacterial effect.

"We can use this information to propose the medicinal application of certain natural clays, especially in wound healing," says Williams.

Chronic, non-healing wounds, adds Morrison, are usually more alkaline (vs. acidic) than healthy skin. The pH of normal skin is slightly acidic, which keeps numbers of bacteria low.

"Antibacterial clays can buffer wounds to a low [more acidic] pH," says Williams, like other accepted chronic wound treatments, such as acidified nitrate. "The clays may shift the wound environment to a pH range that favors healing, while killing invading bacteria."

The Oregon clays could lead to the discovery of new antibacterial mechanisms, she says, "which would benefit the health care industry and people in developing nations. A low-cost topical antibacterial agent is quickly needed."

Answers to Buruli ulcers, MRSA and other antibiotic-resistant infections may lie not in a high-tech lab, but in ancient rocks forged in a hot zone: Oregon's once--and perhaps future--volcanoes.

-- Cheryl Dybas, NSF
Investigators
Lynda Williams
Related Institutions/Organizations
Arizona State University

EPA WARNS OF SWIMMING RELATED ILLNESSES

FROM:  U.S. ENVIRONMENTAL PROTECTION AGENCY 

Human Health

Most of the time when beaches are closed or advisories are issued, it's because the water has high levels of harmful microorganisms (or microbes) that come from untreated or partially treated sewage: bacteria, viruses, or parasites. We also use the word "pathogens" when they can cause disease in humans, animals, and plants.
Illnesses.

hildren, the elderly, and people with weakened immune systems are most likely to develop illnesses or infections after coming into contact with polluted water, usually while swimming. The most common illness is gastroenteritis, an inflammation of the stomach and the intestines that can cause symptoms like vomiting, headaches, and fever. Other minor illnesses include ear, eye, nose, and throat infections

Fortunately, while swimming-related illnesses are unpleasant, they are usually not very serious - they require little or no treatment or get better quickly upon treatment, and they have no long-term health effects. In very polluted water, however, swimmers can sometimes be exposed to more serious diseases like dysentery, hepatitis, cholera, and typhoid fever.

Most swimmers are exposed to waterborne pathogens when they swallow the water. People can get some infections simply from getting polluted water on their skin or in their eyes. In rare cases, swimmers can develop illnesses or infections if an open wound is exposed to polluted water.

Not all illnesses from a day at the beach are from swimming. Food poisoning from improperly refrigerated picnic lunches may also have some of the same symptoms as swimming-related illnesses, including stomachache, nausea, vomiting, and diarrhea.

It is also possible that people may come into contact with harmful chemicals in beach waters during or after major storms, especially if they swim near what we call “outfalls,” where sewer lines drain into the water. You can learn more about this by visiting our web site for stormwater.

Finally, the sun can hurt you if you're not careful. Overexposure can cause sunburn, and over time, it can lead to more serious problems like skin cancer. The sun can also dehydrate you and cause heat-related illnesses like heat exhaustion, muscle cramps, and heat stroke. Learn more about sun safety at our SunWise site or heat-related illnesses at the Centers for Disease Control and Prevention site.

How to Stay Safe

There are several things you can do to reduce the likelihood of getting sick from swimming at the beach. First, you should find out if the beach you want to go to is monitored regularly and posted for closures or swimming advisories. You are less likely to be exposed to polluted water at beaches that are monitored regularly and posted for health hazards.

In areas that are not monitored regularly, choose swimming sites in less developed areas with good water circulation, such as beaches at the ocean. If possible, avoid swimming at beaches where you can see discharge pipes or at urban beaches after a heavy rainfall.

To find out about the beaches you want to visit, contact the local beach manager.

Since most swimmers are exposed to pathogens by swallowing the water, you will be less likely to get sick if you wade or swim without putting your head under water.

IMMUNITY GENES FOUND IN SEA FANS

Photo Shows Sea Fan In Back.  Credit:  U.S. NOAA

FROM:  NATIONAL SCIENCE FOUNDATION

Sick Sea Fans: Undersea "Doctors" to the Rescue

Scientists discover genes involved in immunity of sea fans to coral diseases
Like all of us, corals get sick. They respond to pathogens (disease-causing microbes) and recover or die. But unlike us, they can't call a doctor for treatment.

Instead, help has arrived in the form of scientists who study the causes of the corals' disease, and the immune factors that might be important in their response and resistance.

With support from the National Science Foundation (NSF), scientists Drew Harvell and Colleen Burge of Cornell University and their colleagues have developed a catalog of genes that, the researchers say, will allow us to better understand the immune systems of corals called sea fans.

The marine ecologists have trained their undersea eyes on a particular sea fan species, Gorgonia ventalina, or the purple sea fan, found in the western Atlantic Ocean and the Caribbean Sea.

The team has monitored sea fan health in the Florida Keys, Mexican Yucatan and Puerto Rico for the past 15 years. The most recent research, in collaboration with Ernesto Weil of the University of Puerto Rico, is underway on reefs at La Parguera, Puerto Rico.

Gorgonia ventalina is a fan-shaped coral with several main branches and a latticework of smaller branches. Its skeleton is composed of calcite and gorgonian, a collagen-like compound. Purple sea fans often have smaller, accessory fans growing sideways out of their main fans.

These large sea fans fare best near shore in shallow waters with strong waves and on deeper outer reefs with strong currents, down to a depth of about 50 feet. Small polyps on the graceful fans catch plankton drifting by on fast-flowing currents.

Turning (more) purple

Life as a purple sea fan isn't always easy. The coral may be attacked by the fungus Aspergillus sydowii, which causes the disease aspergillosis.

It results in damaged patches on the fan, extreme purpling of tissues and sometimes death. Several outbreaks of aspergillosis have occurred in the Caribbean; corals in stressful conditions such as warming waters may be especially susceptible.

"Diseases and climate change are very tightly linked," says Mike Lesser, program director in NSF's Division of Ocean Sciences, which funds the research along with the joint NSF-National Institutes of Health Evolution and Ecology of Infectious Diseases (EEID) Program.

"The role of climate change in diseases is important," Lesser says, "for understanding the spread of infectious diseases in every corner of the globe, including the oceans."

Adds Sam Scheiner, NSF EEID program director, "Human-induced climate change is having profound effects on many parts of the world. As this research shows, coral reefs are being decimated by the combination of climate change and infectious diseases."

Undersea "doctors" come to sea fans' aid

Harvell agrees.

In a paper published earlier this year in The Annual Review of Marine Science, Harvell, Burge and other scientists reviewed climate change influences on marine infectious diseases.

Now the scientists are using the purple sea fan as a model for studying ocean diseases. "We're looking at microbial infection, pathways of defense and the health of this sea fan in the face of warming waters and climate change," says Harvell.

"All animals on Earth--from humans to fish to corals--are susceptible to infection by pathogens that cause illness," she says. "What we hope to answer is: How widespread are these infections? Why do they happen? And, what can we do about them?"

Coral reefs are declining worldwide. Even very old coral colonies in remote locations are dying. "Disease-related deaths are caused in part by pathogens alone and in part by interactions between pathogens and climate change," says Burge.

Many of these pathogens are unidentified, leaving sea fans and their coral relatives at high risk.

But the mystery is slowly being solved.

The scientists have discovered two pathogens in purple sea fans. The microbes are being cultured and used to examine how sea fans' immune systems work.

Past is prologue?

A look back a decade or more may provide clues to the present--and the future--for sea fans.

From 1996 through 2004, thousands of sea fans in the Caribbean died of aspergillosis. Many survived, however, and appear resistant to further attack.

But they're far from home free.

Purple sea fans are now being infected by a new pathogen, called Aplanochytrium. Burge was the first to isolate and culture the microbe from a sick sea fan.

Aplanochytrium is a member of an order of lethal microbes known as Labyrinthulomycetes. It grows faster at warmer temperatures, leaving sea fans in "hot water."

Corals don't have "immune memory," such as the T cells and antibodies found in humans. Instead they have an ancient defense system called the innate immune system.

Studying sea fans' immunity through their genes is an important step in protecting them, says Burge.

"We used molecular biology and bioinformatics--a combination of biology, computer science and information technology--to make a set of the genes' messages, called transcripts," she says. "Then we characterized these messages, which are known collectively as a transcriptome."

The results, reported this month in a paper in the journal Frontiers in Physiology, are the first to show which genes are activated in response to pathogens in sea fans. Co-authors of the paper are Burge, Harvell and Morgan Mouchka of Cornell, and Steven Roberts of the University of Washington.

Message in a (genetic) bottle

The purple sea fan may hold messages for the oceans, and for us, but the messages come in a genetic bottle.

The scientists studied what's called messenger RNA, which transfers genetic messages, in sea fans exposed to Aplanochytrium, comparing it with that of unexposed sea fans.

They found that the sea fans' genes hold clues to questions such as how the fans recognize and kill pathogens, and how they repair injured tissues.

The scientists are increasing the sea fan genetic "catalog" by adding genes expressed, or turned on, in response to record-breaking Caribbean Sea temperatures in 2010.

The researchers, working in Puerto Rico with Weil and Laura Mydlarz of the University of Texas at Arlington, assessed the effect of the 2010 Caribbean coral bleaching event, as it's known, on sea fans' genes and immune function.

The study compared immune system genes in a heat-sensitive coral species, Orbicella annularis, the boulder star coral, with that of Gorgonia ventalina.

The purple sea fan was thought to be resilient to the stresses of warming waters. But Gorgonia ventalina, the scientists found, is also susceptible to the double whammy of disease and warming.

-- Cheryl Dybas, NSF

WHY ARE DISEASES NASTY TO THEIR HOSTS?

House Finch.  Credit:  Wikimedia.

FROM: NATIONAL SCIENCE FOUNDATION
Evolution in the Blink of an Eye
A disease in songbirds has rapidly evolved to become more harmful to its host at least twice in two decades, scientists report.

The research offers a model to help understand how diseases that threaten humans may change in virulence as they become more prevalent in a host population.

"Everybody who's had the flu has probably wondered at some point: 'Why do I feel so bad?'" said Dana Hawley of Virginia Polytechnic Institute, lead author of a paper on the results published today in the journal PLOS Biology.

"That's what we're studying: Why do pathogens cause harm to the hosts they depend upon? And, why are some life-threatening, while others only give you the sniffles?"

Disease virulence is something of a paradox.

"The jumping of a pathogen to a new host, such as bird flu jumping to humans, is just the first step of disease emergence," said Sam Scheiner, National Science Foundation (NSF) program director for the joint NSF‒National Institutes of Health Ecology and Evolution of Infectious Diseases Program, which funded the research.

"The subsequent evolution of that pathogen in its new host can be critical to determining further [pathogen] spread," Scheiner said.

"This study is the first to confirm predictions that pathogens may evolve to become more deadly. The results are important for planning responses to events such as the bird flu outbreak in China."

To spread, viruses and bacteria must reproduce in great numbers. But as their numbers increase inside a host's body, the host gets more and more ill.

So a highly virulent disease runs the risk of killing or debilitating its hosts before the hosts can transmit the bug along. But sometimes pathogens find the right balance through evolution. The new study shows that can happen in just a few years.

Hawley and co-authors studied house finch eye disease, a form of conjunctivitis, or pinkeye, caused by the bacteria Mycoplasma gallisepticum.

It first appeared around Washington, D.C., in the 1990s. The house finch is native to the Southwest but has spread to towns and backyards across North America.

The bacteria are not harmful to humans, which makes them a good model for studying the evolution of dangerous diseases such as SARS, Ebola and avian flu.

"There's an expectation that a very virulent disease will become milder over time, to improve its ability to spread," said André Dhondt, director of bird population studies at Cornell University. "Otherwise, it just kills the host and that's the end of it for the organism.

"House finch eye disease gave us an opportunity to test this--and we were surprised to see it actually become worse rather than milder."

The researchers used frozen bacterial samples taken from sick birds in California and along the Eastern Seaboard on five dates between 1994 and 2010, as the pathogen was evolving and spreading.

The samples came from an archive maintained by co-author David Ley of North Carolina State University, who first isolated and identified the causative organism.

The team experimentally infected wild-caught, house finches, then measured how sick the birds got with each sample. The researchers kept the birds in cages as they fell ill then recovered (none of the birds died from the disease).

Contrary to expectations, the biologists found that in both regions--California and the Eastern Seaboard--the disease had evolved to become more virulent over time.

Birds exposed to later disease strains developed more swollen eyes that took longer to heal.

A less-virulent strain spread westward across the continent. Once established in California, however, the bacteria again began evolving higher virulence.

In evolutionary terms, some strains of the bacteria were better adapted to spreading across the continent, while others were more suited to becoming established in a more localized area.

"For the disease to disperse westward, a sick bird has to fly farther, and survive for longer, to pass on the infection," Hawley said. "That will select for strains that make the birds less ill.

"But when it gets established in a new location, there are lots of other potential hosts, especially around bird feeders. It can evolve toward a nastier illness because it's getting transmitted more quickly."

House finch eye disease was first observed in 1994 when birdwatchers reported birds with weepy, inflamed eyes as part of Project Feederwatch at Cornell University.

Though the disease does not kill birds directly, it weakens them and makes them easy targets for predators.

The disease quickly spread south along the East Coast, then north and west across the Great Plains and down the West Coast. By 1998 the house finch population in the eastern United States had dropped by half--a loss of an estimated 40 million birds.

Birdwatchers can do their part to help house finches and other backyard birds by washing their feeders in a 10 percent bleach solution twice a month.

Along with Hawley, Dhondt and Ley, the paper's authors include Erik Osnas and Andrew Dobson of Princeton University, and Wesley Hochachka of the Cornell Lab of Ornithology.

-NSF-