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