NSF FUNDS STUDYING ECO-EPIDEMOLOGY OF LEPTOSPIROSIS

FROM:  NATIONAL SCIENCE FOUNDATION
Field fever, harvest fever, rat catcher's yellows: Leptospirosis by any name is a serious disease

Infection is more prevalent in lower-income tropical areas
Rat catcher's yellows, field fever, harvest fever, black jaundice.

All are names for the same disease, leptospirosis, an infection caused by corkscrew-shaped bacteria called Leptospira.

Symptoms range from mild--headaches, muscle aches, fever--to more severe conditions, such as meningitis and bleeding from the lungs.

Looking for leptospirosis

"Leptospira bacteria are maintained through a complex transmission cycle," write scientist Claudia Munoz-Zanzi of the University of Minnesota and colleagues in a 2014 paper in the American Journal of Tropical Medicine.

"Humans and other mammals, domestic and wild, become infected after contact with urine from an infected host, or Leptospira-contaminated water or damp soil."

Some 7 to 10 million people contract leptospirosis each year. The disease is most prevalent in tropical areas, but may be found almost anywhere that's warm and wet.

In the developed world, leptospirosis occurs in people involved in outdoor activities, such as canoeing and kayaking in warm places. In developing countries, the disease largely happens to farmers and poorer people who live in cities.

Infection with Leptospira is linked with agricultural practices, fouling of household or recreational water, poor housing and waste disposal, and changes in the density or proximity of infected animals such as rodents, domestic animals like dogs and wildlife.

Rodents most common carriers

Rodents are the most common reservoirs of Leptospira, says Munoz-Zanzi.

With a grant from the National Science Foundation (NSF)-National Institutes of Health-U.S. Department of Agriculture Ecology and Evolution of Infectious Diseases (EEID) program, Munoz-Zanzi is studying the eco-epidemiology of leptospirosis.

Awards through the EEID program fund scientists to study how large-scale environmental events--such as habitat destruction and climate variability--alter the risks of viral, parasitic and bacterial diseases.

Munoz-Zanzi's goal is to improve knowledge of the social, epidemiological and ecological factors influencing leptospirosis in South America. She and colleagues are working to identify intervention strategies to reduce the disease's effect on the health of humans and other animals.

South-central Chile: a perfect home for Leptospira?

The study is taking place in the Los Rios region of south-central Chile. The area's climate is moderate, with an economy that's based on farming, agriculture, forestry and tourism.

Most of the region's human population is concentrated in a few urban centers, with the rest scattered in small towns or villages and farm areas.

Munoz-Zanzi's research involves contrasting leptospirosis in three community types: urban slums, rural villages, and farms.

Initial findings from the research showed that 20 percent of leptospirosis starts with rodents, including rats and mice, inside households and in other environments in populated areas.

Leptospira-carrying rodents turned out to be more abundant in rural villages than slums and farms.

"Social factors can be important causes of diseases," says Sam Scheiner, NSF EEID program director. "This study shows that the type of community can determine the presence of rats and mice that are disease-carriers. The results have implications for the control of many infectious diseases."

Danger in a puddle

"Because Leptospira live in water and soil," Munoz-Zanzi says, "the environment plays a key role in transmission in household pets, farm animals and people."

When the scientists collected water from puddles, containers, animal troughs, rivers, canals and drinking water, all showed contamination with Leptospira.

In households where puddles were found along with signs of rodent infestations, leptospirosis was common.

"However," says Munoz-Zanzi, "that was true only in lower income houses."

Some 19 percent of samples from these households--most from locations with warmer temperatures, and many with dogs as pets--tested positive.

Community setting important

The scientists are now examining leptospirosis in dogs and livestock, as well as in humans. They're integrating molecular, epidemiological and other data to gain insights into patterns of infection in various community types.

"The more we understand about this disease," says Munoz-Zanzi, "the more we realize the importance of the local community setting."

Ongoing efforts, she says, include the use of mathematical models to develop recommendations for disease control that's locally relevant. The scientists hope to provide people living in the most affected areas with tools to decrease the effects of leptospirosis.

In the meantime, how can people avoid contracting the disease?

"Wear protective equipment to prevent contact with potentially infected animals and environments," says Munoz-Zanzi, "wash after any such contact, and reduce rodents in places where people live and work."

Crowded tropical conditions where rats and mice freely run from house to house may herald another unwanted guest: Leptospira.

-- Cheryl Dybas, NSF

LOOKING TO CURE ANTIBIOTIC RESISTANCE

FROM:  NATIONAL SCIENCE FOUNDATION
Researcher studies how to prevent antibiotic resistance
Solution could be in bacterial protein called UmuD

The widespread and indiscriminate use of antibiotics has prompted many bacteria to mutate, an adaptation that often renders the drugs useless. The increasing threat of resistance worries infectious disease experts who fear that the era of public health successes brought by the introduction of antibiotics in the 1940s is seriously eroding, or soon even may be at an end.

But what if science could improve existing antibiotics in such a way as to not only destroy bacteria, but prevent them from mutating?

At least one research team, in seeking to better understand bacterial mutation, may provide scientific answers that ultimately could lead to thwarting the organisms' ability to mutate, thus blunting the increasing threat of antibiotic resistance.

"The idea would be a one-two punch," says Penny Beuning, an associate professor of chemistry and chemical biology at Northeastern University's college of science. "We need a good therapeutic target that will both kill the bacteria and prevent mutagenesis."

To be sure, the approach almost certainly is years away. Still, the National Science Foundation (NSF)-funded scientist thinks it may be possible. She and her colleagues are studying an important bacterial protein known as UmuD that regulates mutagenesis and may provide important clues about how to stop the process that eventually results in antimicrobial resistance.

Using the bacterium E. coli as a model, she has learned that UmuD interacts with the machinery that replicates DNA, and, when altered, may provide the switch that triggers mutation. UmuD exists in two forms, a full length version when first expressed, and later, if DNA is damaged, a much shorter form. It is this shorter version that allows bacteria to mutate.

Once there is DNA damage, "there is an SOS response, and the levels of some specific proteins go up," she says. "There is a massive stress response, and UmuD responds by cutting its arms off."

In cells where only the full-length version of the protein is present, the bacteria cannot mutate. "But when it forms its shorter self, the cells are mutable," she says.

The fact that UmuD is not present outside bacteria makes it a viable antibiotic target.

"The hope would be to find something that targets UmuD together with an existing antibiotic to prevent bacteria from mutating and developing a resistance to that particular drug," she says. "Among the things we have been looking at: how does UmuD work, and what controls the cleavage of the arms?"

Beuning is conducting her research under an NSF Faculty Early Career Development (CAREER) grant awarded in 2009 under the American Recovery and Reinvestment Act. The award supports junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organization. NSF is funding her work with $994,655 over five years.

Beuning specifically is looking at the cleavage process of UmuD using gel electrophoresis, which separates proteins according to size.

"UmuD is a small protein--139 amino acids--which loses 24 amino acids from the arm. So it goes from 139 to 115," she says. "We can observe this difference with electrophoresis, allowing us to determine how different conditions or other proteins might affect UmuD cleavage."

The team is studying different UmuD protein interactions in the lab, using biochemistry to see when and how different proteins bind to one another. Essentially "we light up the proteins and measure how they change when other proteins bind, using a method called FRET, which stands for fluorescence resonance energy transfer," she says.

"This measures energy transfer between two proteins using light emission," she adds. "The proteins have to be close to each other for energy transfer to occur, so it's a way of detecting whether two things bind to each other. People often call the technique a molecular ruler, because it can be used to measure precise distances, but we use it simply to measure proximity."

Using FRET, they discovered that UmuD prevents specific protein interactions in the replication process. That is, it stops or slows down replication by keeping two proteins that need to interact for replication from binding to each other. "Protein-protein interactions are generally hard to target with drugs, but the approach has some potential," she says.

They also use another technique that measures how floppy or flexible proteins are by putting them in heavy water and measuring how much heavier the protein gets as it trades its regular hydrogens with heavy hydrogens from the heavy water. "The floppier parts swap out the hydrogens faster than the less floppy parts," she says.

As part of the grant's education component, she has up to ten undergraduates--as well as local high school students and teachers--working in her research lab. Several students have worked in her lab as part of Northeastern's signature co-op program, in which students work full-time for six months in positions related to their career goals.

Also, she teaches an upper level chemical biology class to undergraduates, and created a lab research project for the students that takes place during half of the semester that actually involves them directly in her mutagenesis research.

"A lot of these students had not yet conducted any research, so they were really motivated by the idea of doing something that someone would use as part of a bigger project," she says. "Particularly at Northeastern, where co-op is such a large part of the culture, it is fun to take advantage of the laboratory as the ultimate in experiential education.”

-- Marlene Cimons, National Science Foundation
Investigators
Penny Beuning
Related Institutions/Organizations

HUNTING FOR LEPTOSPIRA BACTERIA

FROM:  THE NATIONAL SCIENCE FOUNDATION
Field fever, harvest fever, rat catcher's yellows: Leptospirosis by any name is a serious disease

Infection is more prevalent in lower-income tropical areas
Rat catcher's yellows, field fever, harvest fever, black jaundice.

All are names for the same disease, leptospirosis, an infection caused by corkscrew-shaped bacteria called Leptospira.

Symptoms range from mild--headaches, muscle aches, fever--to more severe conditions, such as meningitis and bleeding from the lungs.

Looking for leptospirosis

"Leptospira bacteria are maintained through a complex transmission cycle," write scientist Claudia Munoz-Zanzi of the University of Minnesota and colleagues in a 2014 paper in the American Journal of Tropical Medicine.

"Humans and other mammals, domestic and wild, become infected after contact with urine from an infected host, or Leptospira-contaminated water or damp soil."

Some 7 to 10 million people contract leptospirosis each year. The disease is most prevalent in tropical areas, but may be found almost anywhere that's warm and wet.

In the developed world, leptospirosis occurs in people involved in outdoor activities, such as canoeing and kayaking in warm places. In developing countries, the disease largely happens to farmers and poorer people who live in cities.

Infection with Leptospira is linked with agricultural practices, fouling of household or recreational water, poor housing and waste disposal, and changes in the density or proximity of infected animals such as rodents, domestic animals like dogs and wildlife.

Rodents most common carriers

Rodents are the most common reservoirs of Leptospira, says Munoz-Zanzi.

With a grant from the National Science Foundation (NSF)-National Institutes of Health-U.S. Department of Agriculture Ecology and Evolution of Infectious Diseases (EEID) program, Munoz-Zanzi is studying the eco-epidemiology of leptospirosis.

Awards through the EEID program fund scientists to study how large-scale environmental events--such as habitat destruction and climate variability--alter the risks of viral, parasitic and bacterial diseases.

Munoz-Zanzi's goal is to improve knowledge of the social, epidemiological and ecological factors influencing leptospirosis in South America. She and colleagues are working to identify intervention strategies to reduce the disease's effect on the health of humans and other animals.

South-central Chile: a perfect home for Leptospira?

The study is taking place in the Los Rios region of south-central Chile. The area's climate is moderate, with an economy that's based on farming, agriculture, forestry and tourism.

Most of the region's human population is concentrated in a few urban centers, with the rest scattered in small towns or villages and farm areas.

Munoz-Zanzi's research involves contrasting leptospirosis in three community types: urban slums, rural villages, and farms.

Initial findings from the research showed that 20 percent of leptospirosis starts with rodents, including rats and mice, inside households and in other environments in populated areas.

Leptospira-carrying rodents turned out to be more abundant in rural villages than slums and farms.

"Social factors can be important causes of diseases," says Sam Scheiner, NSF EEID program director. "This study shows that the type of community can determine the presence of rats and mice that are disease-carriers. The results have implications for the control of many infectious diseases."

Danger in a puddle

"Because Leptospira live in water and soil," Munoz-Zanzi says, "the environment plays a key role in transmission in household pets, farm animals and people."

When the scientists collected water from puddles, containers, animal troughs, rivers, canals and drinking water, all showed contamination with Leptospira.

In households where puddles were found along with signs of rodent infestations, leptospirosis was common.

"However," says Munoz-Zanzi, "that was true only in lower income houses."

Some 19 percent of samples from these households--most from locations with warmer temperatures, and many with dogs as pets--tested positive.

Community setting important

The scientists are now examining leptospirosis in dogs and livestock, as well as in humans. They're integrating molecular, epidemiological and other data to gain insights into patterns of infection in various community types.

"The more we understand about this disease," says Munoz-Zanzi, "the more we realize the importance of the local community setting."

Ongoing efforts, she says, include the use of mathematical models to develop recommendations for disease control that's locally relevant. The scientists hope to provide people living in the most affected areas with tools to decrease the effects of leptospirosis.

In the meantime, how can people avoid contracting the disease?

"Wear protective equipment to prevent contact with potentially infected animals and environments," says Munoz-Zanzi, "wash after any such contact, and reduce rodents in places where people live and work."

Crowded tropical conditions where rats and mice freely run from house to house may herald another unwanted guest: Leptospira.

-- Cheryl Dybas, NSF

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

NSF ARTICLE: TESTING FOR PATHOGENS

FROM:  NATIONAL SCIENCE FOUNDATION 

Testing for pathogens

Innovation Corps researchers focus on medical applications rather than food safety in response to customer needs

When Sunny Shah and his research colleagues at the University of Notre Dame developed a new diagnostic tool for detecting the presence of bacteria, viruses and other pathogens, they assumed that the food industry would be the perfect market.

It made sense, particularly amid ongoing concerns over food safety. The test could identify, among other things, E. coli 0157, which has caused a number of deadly outbreaks in the United States, as well as the bacterium responsible for brucellosis, a disease caused by eating undercooked meat or unpasteurized dairy products.

Their test was accurate and inexpensive. It just wasn't fast enough.

"Even though we could provide a cheaper test than what is already available, they said they would be willing to pay more for a faster test," Shah says, referring to his conversations with representatives from food processing plants, health agencies and food testing labs. "They said we needed to produce results within two hours, not two days, because they wouldn't be able to ship anything out, and had to pay for refrigeration, while waiting for test results."

So the National Science Foundation (NSF)-funded scientist switched his focus--he likes to call it a "pivot"--from food safety to medical applications. In addition to food-borne bacteria, the test also can recognize the virus that causes Dengue fever, potentially valuable for surveillance activities both here and abroad, and human papillomavirus (HPV), which is linked to cervical and oral cancers.

Shah, who also is assistant director for the ESTEEM graduate program, which exposes those with STEM (science, technology, engineering, and mathematics) backgrounds to business and entrepreneurial courses, received $50,000 in 2013 from NSF's Innovation Corps (I-Corps) program. I-Corps helps scientists assess how, and whether, they can translate their promising discoveries into viable commercial products.

The award supports a set of activities and programs that prepare scientists and engineers to extend their focus beyond the laboratory into the commercial world, with the idea of providing near-term benefits for the economy and society.

It is a public-private partnership program that teaches grantees to identify valuable product opportunities that can emerge from academic research, and offers entrepreneurship training to student participants.

Although things did not turn out as originally planned in this case, Shah's experience nevertheless actually embodies the I-Corps philosophy, since one of its major goals is to mentor scientists in ways that allow them to evaluate the commercial potential of their discoveries, and send them in different directions if necessary to ensure their research ends up in the best possible place to do the most good at an affordable price.

"It doesn't matter what we, as researchers, think is the value of our technology," Shah says. "It's what the customer thinks that is important and the only way to identify this customer need is by getting out and interviewing them."

NSF also earlier supported the research that developed the test in 2011. Shah's research colleagues on this project include Hsueh-Chia Chang, professor of chemical and biomolecular engineering, Satyajyoti Senapati, research assistant professor, and Zdenek Slouka, postdoctoral associate in the Chang group. For the I-Corps grant, Kerry Wilson, managing director of Springboard Engineers, played the role of the business mentor, while Shah was the entrepreneurial lead

The test uses a biochip that can detect the DNA or RNA of a particular pathogen.

"Every pathogen has a unique biomarker, and what we do is put a probe on our biochip that captures that biomarker," Shah says. "If the sample has that particular pathogen, then its biomarker will bind to this probe and give us a signal. There are changes in the electrical properties, so it gives us a visual electrical signal that can easily be translated into a target present/absent signal."

Each chip is programmed for a specific pathogen, "but in the future we hope to develop what we call a multiplex biochip that can detect numerous pathogens all on the same device," Shah adds.

The plan now is to develop the tool for future use by dentists to test their patients during office visits for early detection of HPV-related oral cancer before there are visible signs of disease.

"Usually dentists now just examine you visually for lesions, but this would be a sample swab that could give you advance warning," he says.

The test also might be useful as a diagnostic tool for food-borne disease after infection, that is, in testing an already ill patient's blood, he says.

The team recently received a National Institutes of Health grant to study a possible future surveillance role for the test in screening mosquitoes for the presence of Dengue Fever.

"This is not a huge problem for the United States, although there have been a number of cases in parts of Florida in recent years, but it is an issue in South America, Brazil and India, and other areas, " he says.

The impact of I-Corps allowed Shah to make the transition. "Knowing the market and the customer early is extremely important in the technology commercialization process," he says. The program helped him to "quickly assess a particular market to identify customer need and be ready to pivot from one market to another, if needed."

-- Marlene Cimons, National Science Foundation
Investigators
Sunny Shah
Li-Jing Cheng
Hsueh-Chia Chang
Satyajyoti Senapati
Related Institutions/Organizations
University of Notre Dame

COMPLAINT FILED AGAINST MICHIGAN CHEESE FACTORY FOR DISTRIBUTING ADULTERATED CHEESE PRODUCTS

FROM:  U.S. JUSTICE DEPARTMENT 

Friday, August 8, 2014

United States Files Enforcement Action Against Michigan Cheese Company and Owners to Stop Distribution of Adulterated Cheese Products

A civil complaint was filed today in federal court in Michigan against S. Serra Cheese Company of Clinton Township, Michigan, and its owners, Stefano and Fina Serra, to prevent the distribution of adulterated cheese, announced Assistant Attorney General Stuart F. Delery of the Justice Department’s Civil Division.

S. Serra Cheese Company manufactures and distributes several varieties of Italian cheeses, such as ricotta, provolone, mozzarella and primo sale.  The complaint alleges that the company’s Italian cheeses are manufactured in insanitary conditions, and that the company’s procedures are inadequate to ensure the safety of its products.  The department filed the injunction action in the Eastern District of Michigan at the request of the U.S. Food and Drug Administration (FDA).

“The presence of potentially harmful pathogens in food and processing facilities poses a serious risk to the public health,” said Assistant Attorney General Delery.  “The Department of Justice will continue to bring enforcement actions against food manufacturers who do not follow the necessary procedures to comply with food safety laws.”

According to the complaint, two FDA inspections performed in 2013 revealed that the company’s cheese is adulterated within the meaning of the Food, Drug and Cosmetic Act because it is prepared, packed or held under insanitary conditions in which it may have become contaminated with filth or rendered injurious to health.  The complaint alleges, for example, that the company repeatedly failed to reduce the risk of contamination from two potentially dangerous types of bacteria: Escherichia coli (E. coli) and Listeria innocua (L. innocua).

Although the strains of E. coli found in cheese samples collected from the company’s facility were n on-pathogenic, their presence indicates that the facility is insanitary and contaminated with filth.  In addition, t he presence of L. innocua indicates insanitary conditions and a work environment that could support the growth of L. monocytogenes, an organism that poses a life-threatening health hazard because it is the causal agent for the disease listeriosis, a serious encephalitic disease.  The presence of L. innocua in the company’s facility demonstrates the potential for the presence of L. monocytogenes in the same processing environment.

According to the complaint, the FDA’s most recent inspection in November 2013 revealed insanitary conditions, including the presence of generic, non-pathogenic E. coli and L. innocua and the absence of effective monitoring and sanitation controls in accordance with the current Good Manufacturing Practice requirements for food under federal law.  For example, cleaning and sanitizing operations for utensils and equipment were not performed in a manner that protects against contamination of food and food contact surfaces.

FDA previously inspected the facility in January 2013.  According to the complaint, at that time, FDA inspectors discovered a number of Good Manufacturing Practice deficiencies.  For example, FDA inspectors noted that the facility was not constructed in such a manner as to allow floors to be adequately cleaned and to be kept clean and in good repair.  The FDA inspectors also observed that the company failed to store raw materials in a manner that protects against contamination.

The government is represented by Trial Attorney Dan Baeza of the Civil Division’s Consumer Protection Branch and Assistant U.S. Attorney Peter Caplan for the Eastern District of Michigan, with the assistance of Assistant Chief Counsel for Enforcement Christopher Fanelli of the Food and Drug Division, Office of General Counsel, Department of Health and Human Services.

A complaint is merely a set of allegations that, if the case were to proceed to trial, the government would need to prove by a preponderance of the evidence.

NSF: RESEARCHERS INVESTIGATE REMARKABLE APPROACH TO DESALINATION

FROM:  NATIONAL SCIENCE FOUNDATION 

Rice scientists reprogram protein pairs; attempt to modify bacterial decisions

Desalination has come a long way, baby.

On Aug. 3, some 330 years ago, a certain Captain Gifford of His Majesty's Ship Mermaid, was asked to conduct onboard his 24-gun Royal Naval vessel what may have been the first government-sponsored, scientific desalination experiment.

Diarist and later Secretary to the Admiralty Commission in England Samuel Pepys wrote to Gifford saying, "Whereas a Proposal has been made to Us of an Engine to be fixed in one of Our Ships for the making an Experiment of producing fresh water (at Sea) out of Salt."

We do not know whether Gifford actually conducted the experiment, but we do know desalination--the pulling of salt, minerals and other contaminants from soil and water--has become a worldwide concern. Population increases, the scarcity of fresh water in arid regions and a greater need for environmental cleanup has scientists scrambling to improve the process.

Researchers at Rice University in Houston, Texas, for example, are computationally investigating ways to rewire one of desalination's most useful tools: Bacteria.

Bacteria as an environmental cleaning agent is based on the microorganisms' ability to sense its environment, consume pollutants, break them down and excrete different, less-harmful substances than the original contaminant. But bacteria's response mechanisms can do many other things such as provide scientifically discrete information, diagnose levels of toxins in food and water, detect poisonous chemicals, report dangerous compounds in the human body and more.

That's why Jose Onuchic and Herbert Levine, co-directors of Rice's Center for Theoretical Biological Physics are working to treat bacteria like computers with the intention of reprograming them to perform specific activities.

The researchers have a plan to modify the proteins responsible for how bacteria respond to external stimuli, triggering the bacteria to predictably "decide" what actions to take when confronted with targeted environmental conditions.

Directed bacterial responses, the researchers believe, could revolutionize bacteria-based environmental cleanup, modern desalination and a host of medical and industrial applications.

The project, "Molecular Underpinnings of Bacterial Decision-Making" is one of a number of high-risk, potentially high-reward projects in the National Science Foundation's INSPIRE program. INSPIRE funds potentially transformative research that does not fit into a single scientific field, but crosses disciplinary boundaries.

"This research project by two highly respected scientists and their colleagues is an excellent example of basic research that can have tremendous societal benefits," says Kamal Shukla, program director in NSF's Division of Molecular and Cellular Biosciences.

The project is co-funded by NSF's Directorates for Biological Sciences and Mathematical and Physical Sciences.

Special molecules...

"The information encoded in the genome not only contains the blueprint for making proteins that fold into unique 3-D structures," says Onuchic explaining the basis of the research, "but also contains rich information about functional protein-protein interactions." Two-component signaling (TCS) systems, found mainly in bacteria, are an example of this idea.

TCS systems are the dominant means by which bacteria sense the environment and carry out appropriate actions. These signaling pathways, determine how bacteria respond to heat, sunlight, toxins, oxygen and other environmental stimuli.

They also regulate characteristics such as how poisonous bacteria are, their ability to produce disease, their nutrient uptake, their ability to yield secondary organic compounds, etc.

"Our research tries to understand and potentially re-engineer two-component signaling systems," says Ryan Cheng, a postdoctoral fellow at Rice working on the project. "A successful understanding of the special molecules that make up these systems would allow us to take them apart like Lego blocks and start building new blocks or circuits to achieve a specific goal."

Earlier this year in a paper published in the Proceedings of the National Academy of Sciences, the researchers revealed a scoring metric they devised to interpret how TCS proteins interact with each other and to predict how signaling modifications might affect TCS systems.

The metric, based on sequence data from the coevolution of TCS proteins, could form a framework for fine tuning TCS signals and/or mix-matching TCS proteins leading to novel bacterial responses.

"Many proteins have evolved to produce specific behaviors under the additional constraint that they physically bind to another protein," says Faruck Morcos, a postdoctoral fellow at Rice, whose research focuses on computational biology and bioinformatics.

"Random mutations that may occur to one protein over geological timescales need to occur alongside mutations to the second protein in order to maintain their ability to interact with one another."

However, when the signal between two proteins that have evolved together is modified or a protein is matched with a non-evolutionary signaling partner, directed responses can occur.

"Hence, by applying methods from statistical physics, one can quantify and extract the statistical connections associated with amino acid coevolution between families of interacting proteins," Morcos says, and determine which proteins can successfully signal each other to produce predetermined outcomes.

Practical applications...

With this operating premise, Onuchic and Levine, along with a small cadre of colleagues, plan to use the framework to engineer new, predictable behaviors in a model bacterium called Bacillus subtilis. Moreover, they plan to use B. subtilis as the prototype for changes in other protein-based systems.

"The potential applications for sanitation engineers are both numerous and profound," says Joshua Boltz, senior technologist and the biofilm technologies practice leader at CH2M HILL, a U.S. engineering company with major sewerage programs in London and Abu Dhabi, as well as clean water projects in the United States, Europe and Canada.

"Using membranes as a desalination tool to separate solids from liquids has emerged as a mature technology that is widely used globally," says Boltz zeroing in on an area where the research could benefit his industry. But, "A key concern with using membranes is their fouling, or a reduction in filtration capacity due to orifice clogging as a result of biofilms."

The researchers at Rice believe they can help reduce the buildup of biofilms in desalination equipment. Biofilms are thin layers of cells that stick to each other on a surface and have the ability to obstruct the flow of liquids in water purification systems.

"It has been shown experimentally that wrinkle formation in the biofilms of B. subtilis result from localized cell death," says Cheng. "Since cell death is regulated by two-component and related signaling systems, the potential for controlling the morphology and mechanical properties of biofilms exists."

The researchers surmise that this can perhaps be accomplished by introducing engineered bacteria to existing biofilms that can mechanically weaken existing biofilms through programmed cell death.

"While our research so far has exclusively dealt with quantifying the degree of interaction between a single pair of TCS proteins, a significant challenge will be to extend this work to make in vivo predictions," says Levine.

"Extending our methodology to complicated systems containing many potentially competing protein-protein interactions, e.g. living systems, will be a significant challenge for us in the future. We hope to extend this methodology to predictively understand how making a specific site-directed mutation affects the characteristics of an organism."

-- Bobbie Mixon,
Investigators
Jose Onuchic
Herbert Levine
Related Institutions/Organizations
William Marsh Rice 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.

THE WORLD OF MICRO-LOCOMOTION

FROM:  NATIONAL SCIENCE FOUNDATION 

Microorganisms: Studying the mechanics of their locomotion

Research has potential for improvements in treating diseases and reproductive health and creating new drug delivery systems

Bacteria often must swim through intricate environments in the human body to get where they need to go. How they do it is what fascinates Henry Fu.

"A microbiologist might look at the biology, or biochemical pathways," says Fu, an assistant professor of mechanical engineering at the University of Nevada, Reno. "I am focused on the mechanics, rather than the biology."

Fu's goal is to understand the locomotion of bacteria and other microorganisms, such as sperm and protists, when they swim through such complex substances as mucus or bodily tissues. While both do contain fluid, they are more complicated than water, and bacteria almost certainly need different forces to navigate through them.

"People have tried to understand how they swim through regular water for a very long time, probably 50 or 60 years, but I want to know how this swimming is modified when they are swimming through things more complicated than water, like mucus," says the National Science Foundation (NSF)-funded scientist. "Mucus is more viscous and has elastic properties. People think of mucous as smooth and continuous, but it has a network of fibers. I'm looking at how those fibers interact with the microorganisms."

His work potentially has broad implications in the treatment of diseases, for example, in figuring out ways to block infection by halting a bacterium's movement, even after it has entered the body, such as in Lyme disease, where "bacteria have to burrow through your tissues to get to your bloodstream," Fu says. "Understanding how they do that could be potentially important in order to stop them."

The research also could prove valuable in reproductive health, where "the properties of mucus can affect the likelihood of fertilization," Fu says. "This could be important in treating infertility or contraception, when you could make it easier--or harder--for the sperm to move."

Researchers also could apply mechanical engineering lessons learned toward creating new drug delivery systems, such as nano-robots that could carry chemotherapy through the body to target a growing tumor.

Microorganisms swim by moving parts of their bodies. For example, many swimming bacteria have a tail-like flagellum, which rotates like a propeller, pushing them forward, while some algae have two flagella that "they can use like breast stroke," Fu says. "Part of what I am looking at is how they translate this motion into propelling themselves in the direction of where they want to go."

His research mostly is theoretical--in the computer and with pen and paper--designing models of these swimmers to see how they behave in different environments, and with variations to their swimming motions.

"What we do as modeling is based on well-known fundamental physics laws," he explains. "We could tell the computer the shape of a bacterium and its swimming motion, or how it is rotating, and the properties of the material or fluid it is moving in. We then ask it how it will move, and how much force and energy it will take. We might also ask what might happen if the flagellum or cell had a different shape."

Fu is conducting his research under an NSF Faculty Early Career Development (CAREER) award, which he received in June 2013. The award supports junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education, and the integration of education and research within the context of the mission of their organization. He is receiving $400,003 over five years.

As part of the grant's educational component, he plans to create "Move Like a Microbe," a simulation of microscale microbial locomotion that "will bring the research to life for the public, and K-12 students, by providing a hands-on demonstration of how microorganisms are able to swim, and explain the consequences of microbial locomotion in everyday life," he says.

"Because microorganism are so small and because what they experience in a fluid environment is different from what we expect, this demonstration helps put them in the shoes of a microorganism," he adds. "They can control it, and make it swim, and feel the forces that the microorganism feels--and they will be learning about what it's like to try to swim when you're a tiny thing."

-- Marlene Cimons, National Science Foundation
Investigators
Henry Fu

NSF AND THE VIRUS PIRATES

FROM:  THE NATIONAL SCIENCE FOUNDATION 

Undersea warfare: Viruses hijack deep-sea bacteria at hydro-thermal vents

Unseen armies of viruses and bacteria battle in the deep

More than a mile beneath the ocean's surface, as dark clouds of mineral-rich water billow from seafloor hot springs called hydrothermal vents, unseen armies of viruses and bacteria wage war.

Like pirates boarding a treasure-laden ship, the viruses infect bacterial cells to get the loot: tiny globules of elemental sulfur stored inside the bacterial cells.

Instead of absconding with their prize, the viruses force the bacteria to burn their valuable sulfur reserves, then use the unleashed energy to replicate.

"Our findings suggest that viruses in the dark oceans indirectly access vast energy sources in the form of elemental sulfur," said University of Michigan marine microbiologist and oceanographer Gregory Dick, whose team collected DNA from deep-sea microbes in seawater samples from hydrothermal vents in the Western Pacific Ocean and the Gulf of California.

"We suspect that these viruses are essentially hijacking bacterial cells and getting them to consume elemental sulfur so the viruses can propagate themselves," said Karthik Anantharaman of the University of Michigan, first author of a paper on the findings published this week in the journal Science Express.

Similar microbial interactions have been observed in shallow ocean waters between photosynthetic bacteria and the viruses that prey upon them.

But this is the first time such a relationship has been seen in a chemosynthetic system, one in which the microbes rely solely on inorganic compounds, rather than sunlight, as their energy source.

"Viruses play a cardinal role in biogeochemical processes in ocean shallows," said David Garrison, a program director in the National Science Foundation's (NSF) Division of Ocean Sciences, which funded the research. "They may have similar importance in deep-sea thermal vent environments."

The results suggest that viruses are an important component of the thriving ecosystems--which include exotic six-foot tube worms--huddled around the vents.

"The results hint that the viruses act as agents of evolution in these chemosynthetic systems by exchanging genes with the bacteria," Dick said. "They may serve as a reservoir of genetic diversity that helps shape bacterial evolution."

The scientists collected water samples from the Eastern Lau Spreading Center in the Western Pacific Ocean and the Guaymas Basin in the Gulf of California.

The samples were taken at depths of more than 6,000 feet, near hydrothermal vents spewing mineral-rich seawater at temperatures surpassing 500 degrees Fahrenheit.

Back in the laboratory, the researchers reconstructed near-complete viral and bacterial genomes from DNA snippets retrieved at six hydrothermal vent plumes.

In addition to the common sulfur-consuming bacterium SUP05, they found genes from five previously unknown viruses.

The genetic data suggest that the viruses prey on SUP05. That's not too surprising, said Dick, since viruses are the most abundant biological entities in the oceans and are a pervasive cause of mortality among marine microorganisms.

The real surprise, he said, is that the viral DNA contains genes closely related to SUP05 genes used to extract energy from sulfur compounds.

When combined with results from previous studies, the finding suggests that the viruses force SUP05 bacteria to use viral SUP05-like genes to help process stored globules of elemental sulfur.

The SUP05-like viral genes are called auxiliary metabolic genes.

"We hypothesize that the viruses enhance bacterial consumption of this elemental sulfur, to the benefit of the viruses," said paper co-author Melissa Duhaime of the University of Michigan. The revved-up metabolic reactions may release energy that the viruses then use to replicate and spread.

How did SUP05-like genes end up in these viruses? The researchers can't say for sure, but the viruses may have snatched genes from SUP05 during an ancient microbial interaction.

"There seems to have been an exchange of genes, which implicates the viruses as an agent of evolution," Dick said.

All known life forms need a carbon source and an energy source. The energy drives the chemical reactions used to assemble cellular components from simple carbon-based compounds.

On Earth's surface, sunlight provides the energy that enables plants to remove carbon dioxide from the air and use it to build sugars and other organic molecules through the process of photosynthesis.

But there's no sunlight in the deep ocean, so microbes there often rely on alternate energy sources.

Instead of photosynthesis they depend on chemosynthesis. They synthesize organic compounds using energy derived from inorganic chemical reactions--in this case, reactions involving sulfur compounds.

Sulfur was likely one of the first energy sources that microbes learned to exploit on the young Earth, and it remains a driver of ecosystems found at deep-sea hydrothermal vents, in oxygen-starved "dead zones" and at Yellowstone-like hot springs.

Dick said the new microbial findings will help researchers understand how marine biogeochemical cycles, including the sulfur cycle, will respond to global environmental changes such as the ongoing expansion of dead zones.

SUP05 bacteria, which are known to generate the greenhouse gas nitrous oxide, will likely expand their range as oxygen-starved zones continue to grow in the oceans.

In addition to Anantharaman, Dick and Duhaime, co-authors of the Science Express paper are John Breir of the Woods Hole Oceanographic Institution, Kathleen Wendt of the University of Minnesota and Brandy Toner of the University of Minnesota.

The project was also funded by the Gordon and Betty Moore Foundation and the University of Michigan Rackham Graduate School Faculty Research Fellowship Program.

-NSF-
Media Contacts
Cheryl Dybas, NSF

FDA ANNOUNCES VOLUNTARY PLAN TO END USE OF SOME ANTIBIOTICS IN FARM ANIMALS

Photo From FDA Website.

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 

Phasing Out Certain Antibiotic Use in Farm Animals

The Food and Drug Administration (FDA) is implementing a voluntary plan with industry to phase out the use of certain antibiotics for enhanced food production.
Antibiotics are added to the animal feed or drinking water of cattle, hogs, poultry and other food-producing animals to help them gain weight faster or use less food to gain weight.

Because all uses of antimicrobial drugs, in both humans and animals, contribute to the development of antimicrobial resistance, it is important to use these drugs only when medically necessary. Governments around the world consider antimicrobial-resistant bacteria a major threat to public health. Illnesses caused by drug-resistant strains of bacteria are more likely to be potentially fatal when the medicines used to treat them are rendered less effective.

FDA is working to address the use of “medically important” antibiotics in food-producing animals for production uses, such as to enhance growth or improve feed efficiency. These drugs are deemed important because they are also used to treat human disease and might not work if the bacteria they target become resistant to the drugs’ effects.

“We need to be selective about the drugs we use in animals and when we use them,” says William Flynn, DVM, MS, deputy director for science policy at FDA’s Center for Veterinary Medicine (CVM). “Antimicrobial resistance may not be completely preventable, but we need to do what we can to slow it down.”

FDA is issuing a final guidance document that explains how animal pharmaceutical companies can work with the agency to voluntarily remove growth enhancement and feed efficiency indications from the approved uses of their medically important antimicrobial drug products, and move the therapeutic uses of these products from over-the-counter (OTC) availability to marketing status requiring veterinary oversight.

Once manufacturers voluntarily make these changes, the affected products can then only be used in food-producing animals to treat, prevent or control disease under the order of or by prescription from a licensed veterinarian.

“This action promotes the judicious use of important antimicrobials, which protects public health and, at the same time, ensures that sick and at-risk animals receive the therapy they need,” says CVM Director Bernadette Dunham, DVM, Ph.D. “We realize that these steps represent changes for veterinarians and animal producers, and we have been working to make this transition as seamless as possible.”

Drugs Primarily in Feed

Flynn explains that all the drugs affected by this plan are antibacterial products. They have long been FDA-approved for production (e.g. growth enhancement) purposes as well as for the treatment, control or prevention of animal diseases. Even today, he says, it is not entirely understood how these drugs make animals grow faster. The drugs are primarily added to feed, although they are sometimes added to the animals’ drinking water.

Bacteria evolve to survive threats to their existence. In both humans and animals, even appropriate therapeutic uses of antibiotics can promote the development of drug resistant bacteria. When such bacteria enter the food supply, they can be transferred to the people who eat food from the treated animal.

In 2010, FDA called for a strategy to phase out production use of medically important antimicrobial products and to bring the remaining therapeutic uses under the oversight of a veterinarian. The guidance document that FDA is issuing on Dec. 11, 2013, which was previously issued in draft form in 2012, lays out such a strategy and marks the beginning of the formal implementation period.

The agency is asking animal pharmaceutical companies to notify FDA within the next three months of their intent to voluntarily make the changes recommended in the guidance. Based on timeframes set out in the guidance, these companies would then have three years to fully implement these changes.

To help veterinarians and producers of food-producing animals comply with the new terms of use for these products once the recommended changes are implemented, FDA is proposing changes to the Veterinary Feed Directives (VFD) process. This is an existing system that governs the distribution and use of certain drugs (VFD drugs) that can only be used in animal feed with the specific authorization of a licensed veterinarian. Flynn explains that feed-use antibiotics that are considered medically important and are currently available as OTC products will, as a result of implementation of the guidance document, come under the VFD process.

The proposed changes to the VFD process are intended to clarify the administrative requirements for the distribution and use of VFD drugs and improve the efficiency of the VFD program. Such updates to the VFD process will assist in the transition of OTC products to their new VFD status.

Why Voluntary?

Flynn explains that the final guidance document made participation voluntary because it is the fastest, most efficient way to make these changes. FDA has been working with associations that include those representing drug companies, the feed industry, producers of beef, pork and turkey, as well as veterinarians and consumer groups.

"Based on our outreach, we have every reason to believe that animal pharmaceutical companies will support us in this effort," says Michael R. Taylor, FDA's deputy commissioner for foods and veterinary medicine.

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

SUPEROXIDES IN THE DARK

Ocean Sunset.  Credit:  U.S. Navy.

FROM:  NATIONAL SCIENCE FOUNDATION

'Dark Oxidants' Form Away from Sunlight in Lake and Ocean Depths, Underground Soils
New findings overturn understanding of light-dependent environmental oxidants

Breathing oxygen... can be hazardous to your health?

Indeed, our bodies aren't perfect. They make mistakes, among them producing toxic chemicals, called oxidants, in cells. We fight these oxidants naturally, and by eating foods rich in antioxidants such as blueberries and dark chocolate.

All forms of life that breathe oxygen--even ones that can't be seen with the naked eye, such as bacteria--must fight oxidants to live.

"If they don't," says scientist Colleen Hansel of the Woods Hole Oceanographic Institution in Massachusetts, "there are consequences: cancer and premature aging in humans, death in microorganisms."

These same oxidants also exist in the environment. But neutralizing environmental oxidants such as superoxide was a worry only for organisms that dwell in sunlight--in habitats that cover a mere 5 percent of the planet.

That was the only place where such environmental oxidants were thought to exist.

Now researchers have discovered the first light-independent source of superoxide. The key is bacteria common in the depths of the oceans and other dark places.

The bacteria breathe oxygen, just like humans. "And they're everywhere--literally," says Hansel, co-author of a paper reporting the results and published in this week's issue of the journal Science Express.

The result expands the known sources of superoxide to the 95 percent of Earth's habitats that are "dark." In fact, 90 percent of the bacteria tested in the study produced superoxide in the dark.

"Superoxide has been linked with light, such that its production in darkness was a real mystery," says Deborah Bronk of the National Science Foundation's (NSF) Division of Ocean Sciences, which co-funded the research with NSF's Division of Earth Sciences.

"This finding shows that bacteria can produce superoxide in the absence of light."

The bacteria are found "miles beneath the seafloor, in hot fluids coming from underwater volcanoes, in every type of underground soil and throughout deep lake and ocean waters," Hansel says.

The number of these bacteria in a thimble of seawater or soil is greater than the human population of San Francisco. And they're all releasing large amounts of superoxide.

On Earth's surface, "superoxide can kill corals, turning them white," says Hansel. "It can also produce huge fish kills during red tides. But it's not always bad."

It also helps ocean microorganisms acquire the nutrients they need to survive. And superoxide may remove the neurotoxin mercury from the sea, keeping it out of fish and off dinner plates.

The bacteria that produce superoxide could account for the total amount of the chemical in the oceans, Hansel and colleagues say, and are likely the main source in dark environments.

"That's a paradigm shift that will transform our understanding of the chemistry of the oceans, as well as of lakes and underground soils," says Hansel, "and of the life forms that live in and depend on them."

Co-authors of the paper are Julia Diaz and Chantal Mendes of Harvard University, Peter Andeer and Tong Zhang of Woods Hole Oceanographic Institution and Bettina Voelker of the Colorado School of Mines.

-NSF-