OREGON STATE UNIVERSITY

college of veterinary medicine

Protein transport channel offers new target for thwarting pathogen

CORVALLIS, Ore. – A bacterium that attacks people suffering from chronic lung disease and compromised immune systems could be halted by disrupting the distribution channels the organism uses to access the nutrient-rich cytoplasm of its host cell.

The findings by researchers in Oregon State University’s colleges of science and veterinary medicine are important because they suggest a new therapeutic target for one of the leading causes of bacterial infection in patients with HIV/AIDS.

The bacterium is Mycobacterium avium, the most common pathogen among non-tuberculosis mycobacteria. Highly opportunistic, M. avium invades and proliferates within a variety of human cells; it resides in a cytoplasmic vacuole and survives by remodeling its vacuolar compartment and resisting its host’s antimicrobial mechanisms.

“Most bacteria that grow in phagocytic cells export their effector proteins that impair or redirect macrophage function by using a needle-like apparatus that perforates the vacuole membrane and delivers virulence-associated molecules to the cytoplasm,” said co-corresponding author Luiz Bermudez of OSU’s College of Veterinary Medicine. “But mycobacteria don’t have that, so the question has always been, how do all these proteins get exported, how do they cross the vacuole membrane?”

They likely do so because proteins of the pathogen dock to transport proteins of the phagosome in the host cell in a way that allows for the efficient secretion of effector proteins. Co-corresponding author Lia Danelishvili, also of the College of Veterinary Medicine, identified voltage-dependent anion channels as a possible means of exporting those proteins.

“A VDAC is very small, but it can become larger if several VDAC proteins get together through polymerization,” Bermudez said. “We found that yes, mycobacteria use surface proteins to bind to the VDAC. But although we tried to see if the proteins of the mycobacterium were exported by the VDAC, we couldn’t show that. However, we did show that another component of the cell wall of the mycobacterium, lipids, are exported by that mechanism.”

Next up is determining what specific physical and chemical interactions occur to make effector protein transport possible.

“The idea is to find out the mechanism bacteria use to secrete proteins produced in the cells that have important functions in controlling the phagocytic activity that’s supposed to kill them,” Bermudez said.

Findings were recently published in Scientific Reports. 

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Steve Lundeberg, 541-737-4039

Study sheds light on determining surgical margins for feline tumors

CORVALLIS, Ore. – Researchers at Oregon State University are paving the way for more precision in determining surgical margins for an aggressive tumor common in cats by analyzing tissue contraction at various stages of the post-operative examination process. 

The findings are important because inaccuracy in feline injection-site sarcoma surgical margins – the tissue cut out along with the tumor to try to ensure all cancerous cells are removed – can have a negative effect on the patient’s health, whether the margin is bigger or smaller than necessary.

Understanding how margin length decreases from surgery to pathology – because of how the removed tissue shrinks and tumor cells invade surrounding tissues – can lead to better surgical margin planning and in turn a better prognosis, said corresponding author Milan Milovancev, a board-certified veterinary surgeon at OSU’s College of Veterinary Medicine.

“If we can understand the relationship between what the pathologist sees on a slide under a microscope and what the surgeon is taking out in the operating room, and what accounts for the differences between the two, then we can work backward and figure out how much surgical margin to take,” he said.

The pilot study looked at 35- to 55-millimeter surgical margins from five cats with feline injection site sarcoma, or FISS, and found the greatest margin decreases occurred right after excision. It also found the margins tended to be larger than necessary.

“Older studies showed that if you had bigger margins, cats would live longer,” Milovancev said. “The previous margin guidelines of 2 to 3 centimeters had been found to be inadequate, and the new guidelines were 5, which seemed like a big jump and in some of these cats may cause a lot of unnecessary suffering.

“The net take-home is that yes, 2 to 3 centimeters is indeed inadequate, but we didn’t find any tumors getting close to 5 centimeters. We can reduce morbidity by surgically removing what we need to take out and leaving what doesn’t need to be taken out.”

Milovancev notes that future, larger studies that categorize results by factors that might influence tumor-free margin length – such as tumor grade and location – are likely to lead to more refined preoperative surgical planning.

This pilot research builds on an earlier study by Milovancev and collaborators that examined the ability of MRIs and CT angiograms to detect cancerous lesions related to FISS, and another study that looked at three methods for assessing margins for canine mast cell tumors and soft tissue sarcomas.

In the imaging study, neither method definitely determined cancerous lesions from noncancerous ones and, surprisingly to the researchers, more than half the lesions thought to be cancerous on imaging turned out to be benign changes.

In the margin assessment research that involved more than 70 dogs, there was little agreement between the three techniques: imprint cytology, shaved margin histopathology and radial section histopathology.

“We’ll follow up on the dogs and figure out which method best predicted tumor regrowth,” he said. “The methods weren’t aligned in their results, so one of them is better than the other two.”

Findings of the FISS margin length study were recently published in Veterinary Surgery. Collaborators included Jesse Terry, Sarah Nemanic and Christiane Löhr of the OSU College of Veterinary Medicine.

An Intramural Resident Training grant from the college’s Department of Clinical Sciences funded this research.

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Steve Lundeberg, 541-737-4039

Blocking TB germs’ metabolic ‘escape pathways’ may be key to better, shorter treatment

CORVALLIS, Ore. – New research suggests the bacteria that cause tuberculosis alter their metabolism to combat exposure to antimicrobials, and that these metabolic “escape pathways” might be neutralized by new drugs to shorten the troublesome duration of therapy.

The findings are important because the respiratory disease kills nearly 2 million people a year worldwide, and its long treatment regimen leads to poor compliance and, in turn, drug-resistant germs.

Oregon State University scientist Luiz Bermudez estimated that decreasing the time of treatment from six months to three weeks would likely eliminate many of the compliance problems.

His research may be a key step toward that shorter therapy.

About one-third of the global population is infected with the bacteria that cause TB – Mycobacterium tuberculosis, or Mtb – though only a small percentage will develop the actual disease. For those who do, treatment is basically the same now as it was a half-century ago: taking a combination of drugs for six months because the germs do not die easily or quickly.

As Bermudez notes, anyone who’s ever had trouble sticking with a 10-day antibiotic regimen for an ear infection can understand the hurdles in taking multiple medicines for a couple of dozen weeks – especially given the numerous side effects of the TB drugs.

Another compliance issue is that tuberculosis is particularly prevalent in impoverished countries in which patients often live great distances from pharmacies and other medical facilities.

“Because of problems with compliance, you have resistance becoming more and more of an issue,” said Bermudez, a physician and a faculty member in OSU’s College of Veterinary Medicine. “And the second line of drugs is much more toxic than the first line of drugs.”

Bermudez and collaborators at the veterinary college, as well as researchers at Oregon State’s colleges of science and pharmacy and Oregon Health & Science University, took a biology-driven approach to learn how Mtb prolongs survival following exposure to bactericidal concentrations of antimicrobials.

Researchers investigated how the bacteria reacted to each class of anti-TB drug with the goal of making headway toward developing a more-reasoned combination therapy.

They studied the proteomic responses of the bacteria to five compounds – isoniazid, rifampicin, moxifloxacin, mefloquine and bedaquiline – and discovered escape pathways and enzymes associated with changes in metabolic state.

“When we looked at the enzymes carefully, we realized the enzymes being synthesized by the bacteria were enzymes connecting several different metabolic pathways,” Bermudez said. “Then we came up with the idea that maybe what the bacteria were trying to do, in the presence of a bactericidal compound that was threatening their way of living, was use other ways to survive. One of the things we saw, for example, was a shift to an anaerobic metabolism, which makes a lot of drugs inactive and incapable of killing bacteria. 

“The gene inactivation of some of these enzymes results in improved drug efficacy against Mtb,” he said. “The identified proteins may provide powerful targets for development of synergistic drugs aimed to accelerate bacterial killing.”

Bermudez said that using a combination of drugs to treat tuberculosis arose as an attempt to prevent antibiotic resistance.

“But the antibiotics used were never a rational combination of drugs and in some cases they could antagonize each other,” he said. “If we can use another compound that inhibits bacteria from shifting metabolic pathways, then we get a more reliable and desirable synergy of therapy. That might have a significant impact on reducing the time needed for therapy and improving compliance and, consequently, reducing the emergence of resistance.”

Findings were published recently in Antimicrobial Agents and Chemotherapy. The National Institutes of Health supported this research.

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By Steve Lundeberg, 541-737-4039

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Immune system uses gut bacteria to control glucose metabolism

CORVALLIS, Ore. – Researchers at Oregon State University and other institutions have discovered an important link between the immune system, gut bacteria and glucose metabolism – a “cross-talk” and interaction that can lead to type 2 diabetes and metabolic syndrome when not functioning correctly.

The findings, published today in Nature Communications, are one example of how different mammalian systems can affect each other in ways not previously understood.

A better understanding of these systems, researchers say, may lead to new probiotic approaches to diabetes and other diseases.

The research also shows the general importance of proper bacterial functions in the gut and the role of one bacteria in particular – Akkermansia muciniphila -  in helping to regulate glucose metabolism.

This bacteria’s function is so important, scientists say, that it has been conserved through millions of years of evolution to perform a similar function in both mice and humans.

“We’re discovering that in biology there are multiple connections and communications, what we call cross-talk, that are very important in ways we’re just beginning to understand,” said Dr. Natalia Shulzhenko, an assistant professor in the OSU College of Veterinary Medicine, and one of the corresponding authors on this study.

“It’s being made clear by a number of studies that our immune system, in particular, is closely linked to other metabolic functions in ways we never realized. This is still unconventional thinking, and it’s being described as a new field called immunometabolism. Through the process of evolution, mammals, including humans, have developed functional systems that communicate with each other, and microbes are an essential part of that process.”

It had been previously observed that an immune mediator - one type of interferon, or signaling protein called IFN-y – can affect the proper function of glucose metabolism. IFN-y helps fight several pathogens and infections, but a decrease in its levels can lead to improvement in glucose metabolism. However, this actual process has not been understood.

“Before this, no one had a clue exactly how IFN-y affected glucose tolerance,” said Andrey Morgun, an assistant professor in the OSU College of Pharmacy and also a corresponding author on the study. “The involvement of microbes had not really been considered. But with the help of a statistical model and an approach we call a transkingdom network, we were able to pinpoint some likely bacterial candidates.”

The bacteria A. muciniphila, was found to play a critical role in this communication process – in their study, the scientists called it a “missing link.” Research showed that mice specially bred with reduced levels of IFN-y had higher levels of A. muciniphila, and significantly improved glucose tolerance. When IFN-y levels increased, A. muciniphila levels declined, and glucose tolerance was reduced.

Similar observations were also made in humans. It’s been observed, for instance, that athletes who are extremely fit have high levels of the gut bacteria A. muciniphila, which is a mucus-degrading bacteria. The research makes clear that two systems once believed to be functionally separate – immunity and glucose metabolism – are, in fact, closely linked, and the bridge can be provided by gut bacteria.

There’s probably more than one bacteria involved in this process of communication and metabolic control, researchers said. The gut harbors literally thousands of microbes that appear to function almost as a metabolically active organ, emphasizing the critical importance of gut bacterial health.

Bacteria-mediated communication, of course, is just one part of complex human systems – issues such as proper diet, exercise, and appropriate weight control are all still important, the researchers said.

This research was supported by the National Institutes of Health. Other collaborating researchers were from the University of Sao Paulo in Brazil, University of North Carolina, National Institute of Allergy and Infectious Diseases, and Duke University Medical Center. Co-first authors were Renee Greer of the OSU College of Veterinary Medicine and Xiaoxi Dong of the OSU College of Pharmacy.

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Dr. Natalia Shulzhenko, 541-737-1051

natalia.shulzhenko@oregonstate.edu

OSU trustees approve expanding veterinary teaching hospital, renovating Magruder Hall

BEND, Ore. – The Oregon State University Board of Trustees Friday approved the renovation of Magruder Hall to allow OSU’s College of Veterinary Medicine to increase its enrollment and expand the college’s small animal veterinary teaching hospital.

The trustees’ meetings were held on the new OSU-Cascades campus, which opened in September as the state’s first new public university in 50 years.

The $10 million project to expand Magruder Hall will be added to Oregon State’s overall $258 million 2015-17 capital plan.

Plans include a 6,000-square-foot expansion to double the size of the College of Veterinary Medicine’s small animal teaching hospital that presently serves nearly 40 cases per day and has from 45 to 70 people working in it. Over the past four years, the hospital’s case load has increased 15 percent annually. Renovation of Magruder Hall and the expansion of the hospital will enable the college to grow its enrollment by 16 veterinary medicine students.

“This project will directly improve the educational experience of veterinary students by providing improved instructional space, including laboratories for learning, such as anatomy and surgery skills,” said Sue Tornquist, dean of OSU’s College of Veterinary Medicine. “With this project, graduating veterinarians will have training in new and advanced treatment procedures, such as radiation oncology.”

Tornquist said the college will use philanthropic gifts, college funds and tuition revenues from the projected additional student enrollment to pay for the project.

In other business:

 

  • The board approved its annual performance review of OSU President Ed Ray for the past fiscal year;
  • Established guidelines for future presidential searches and selection processes;
  • Adopted a board calendar to guide the work of the board over the next year;
  • Adopted amendments to the university’s investment policy. The amendments enable the university’s vice president for finance and administration to provide quarterly reports regarding the investment of university assets to the board’s Finance and Administration Committee instead of the full board;
  • Approved the termination of a Master of Agriculture program. This master’s program is experiencing low student participation with currently only five students enrolled. The College of Agricultural Sciences plans to develop a new degree program that addresses current and future agricultural issues.

 

Board Chair Pat Reser said that Ray’s performance assessment included input from university, community, Oregon and national higher education constituents. She said Ray is considered a trusted, energetic and strategic leader. “We compliment President Ray on the progress the university has made over the past year and support his focused and continued outstanding leadership of Oregon State University,” Reser said.

The board deferred until its January 2017 meeting consideration of a change in the university’s in the Public University Fund that would have divested university funds from current fossil fuel-related securities and would restrict future investments in fossil fuel-related securities. Oregon State and five other Oregon public universities make up the Public University Fund, which is managed by the Oregon Treasurer’s office. Presently, approximately 1.7 percent of that fund is invested in fossil fuel-related securities.

In deferring action until January, trustees directed university administrators to develop a draft framework that the board could utilize in evaluating decisions about divestiture or other future financial matters.

During the meeting, trustees heard reports from President Ray; officers of the OSU Faculty Senate, the Associated Students of Oregon State University and the Associated Students of Cascades Campus; the chair of the state’s Higher Education Coordinating Commission; and the OSU Foundation regarding the foundation’s strategic plan.

During public comment provided the board, a graduate student in Oregon State’s College of Education, asked trustees to reverse the university’s decision to build OSU’s marine studies building on the Hatfield Marine Sciences Center campus.

On Wednesday, trustees held a public session retreat to learn more about the university’s student success initiative; the cost structure of the university; and future revenue and cost management opportunities.

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Fat, sugar cause bacterial changes that may relate to loss of cognitive function

CORVALLIS, Ore. – A study at Oregon State University indicates that both a high-fat and a high-sugar diet, compared to a normal diet, cause changes in gut bacteria that appear related to a significant loss of “cognitive flexibility,” or the power to adapt and adjust to changing situations.

This effect was most serious on the high-sugar diet, which also showed an impairment of early learning for both long-term and short-term memory.

The findings are consistent with some other studies about the impact of fat and sugar on cognitive function and behavior, and suggest that some of these problems may be linked to alteration of the microbiome – a complex mixture in the digestive system of about 100 trillion microorganisms.

The research was done with laboratory mice that consumed different diets and then faced a variety of tests, such as water maze testing, to monitor changes in their mental and physical function, and associated impacts on various types of bacteria. The findings were published in the journal Neuroscience, in work supported by the Microbiology Foundation and the National Science Foundation.

“It’s increasingly clear that our gut bacteria, or microbiota, can communicate with the human brain,” said Kathy Magnusson, a professor in the OSU College of Veterinary Medicine and principal investigator with the Linus Pauling Institute.

“Bacteria can release compounds that act as neurotransmitters, stimulate sensory nerves or the immune system, and affect a wide range of biological functions,” she said. “We’re not sure just what messages are being sent, but we are tracking down the pathways and the effects.”

Mice have proven to be a particularly good model for studies relevant to humans, Magnusson said, on such topics as aging, spatial memory, obesity and other issues.

In this research, after just four weeks on a high-fat or a high-sugar diet, the performance of mice on various tests of mental and physical function began to drop, compared to animals on a normal diet. One of the most pronounced changes was in what researchers call cognitive flexibility.

“The impairment of cognitive flexibility in this study was pretty strong,” Magnusson said. “Think about driving home on a route that’s very familiar to you, something you’re used to doing. Then one day that road is closed and you suddenly have to find a new way home.”

A person with high levels of cognitive flexibility would immediately adapt to the change, determine the next best route home, and remember to use the same route the following morning, all with little problem. With impaired flexibility, it might be a long, slow, and stressful way home.

This study was done with young animals, Magnusson said, which ordinarily would have a healthier biological system that’s better able to resist pathological influences from their microbiota. The findings might be even more pronounced with older animals or humans with compromised intestinal systems, she said.

What’s often referred to as the “Western diet,” or foods that are high in fat, sugars and simple carbohydrates, has been linked to a range of chronic illnesses in the United States, including the obesity epidemic and an increased incidence of Alzheimer’s disease.

“We’ve known for a while that too much fat and sugar are not good for you,” Magnusson said. “This work suggests that fat and sugar are altering your healthy bacterial systems, and that’s one of the reasons those foods aren’t good for you. It’s not just the food that could be influencing your brain, but an interaction between the food and microbial changes.”

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Kathy Magnusson, 541-737-6923

More horses found with Equine Herpes Virus, including most serious form

CORVALLIS, Ore. – Three more cases have been found in Oregon of horses infected with Equine Herpes Virus 1, or EHV-1, and one animal has the most serious “neurotropic” form of the virus that is far more likely to cause serious, sometimes permanent neurological damage.

An initial case of EHV-1 reported last week, and also being treated in isolation at OSU, only had the more common wild strain of the virus. That horse did show neurologic symptoms, although animals with that strain of EHV-1 more often have a disease that causes respiratory infection or abortion in pregnant mares.

Two more cases have been identified of horses with the wild strain, that are not showing signs of neurologic disease, and they are being treated at their home stables in Polk County. Both forms of EHV-1 are highly contagious to horses, but not transmissible to people.

However, a fourth case has been confirmed with the neurotropic form of EHV-1, veterinary experts say, which increases the seriousness of the current outbreak, and makes it increasingly important that horse owners in Oregon practice strong biosecurity management of their animals.

“About 80 percent of the horses who develop neurologic problems from EHV-1 have the neurotropic form of the virus,” said John Schlipf, a large animal internal medicine specialist with the OSU College of Veterinary Medicine. “It’s a significantly more serious concern. The disease can be fatal, or it can cause lasting neurologic damage that leaves the animal with a permanently reduced level of function.”

The most recent case was brought to OSU’s Lois Bates Acheson Veterinary Teaching Hospital from the Salem area. Both cases are being treated in isolation, and all OSU veterinary teaching hospital facilities are open for business as usual.

The initial case last week was in a horse housed in Marion County that had recently attended events at the Linn County Fairgrounds in Albany on April 16-19. Prior to the development of clinical signs in the initial case and institution of the quarantine, horses housed with the initial case had attended an event at the Oregon Horse Center in Eugene on April 25-26. The newest case was not at the Linn County event, Schlipf said, but had been in contact with other horses that attended.

Since there’s a 10-14 day incubation period for this virus, Schlipf said, it is possible that more horses will be found to be infected. Owners of horses that may be at risk are encouraged to monitor their animals closely for a fever and any signs of respiratory or neurologic disease. More information about the virus and biosecurity recommendations is available online at http://bit.ly/1GNttiS

Early clinical signs of the neurologic form of EHV-1 often begin with the hind limbs and include:

  • Uncoordinated, stumbling movements;
  • An unusual gait;
  • A weak tail tone;
  • Difficulty urinating, and dribbling of urine;
  • Nasal discharge, frequently accompanied by a fever.

The Oregon Department of Agriculture recommends that horses that attended the Albany or Eugene events avoid contact with other horses and have their temperatures monitored twice daily. Temperatures over 101.5 degrees may indicate illness.

Horses with these signs should be isolated from other animals, and owners should contact their veterinarians immediately. EHV-1 can also affect alpacas and llamas, Schlipf said.

“We must reiterate the need for horse owners to practice biosecurity,” Schlipf said. “People handling horses should wash their hands and clothing to reduce spread of a virus. Animals should not share tack, and horses that have traveled or mingled with other animals should be segregated.

“All of these steps can help, and are especially important right now. It may be a while yet before we are out of the woods with this outbreak.”

 

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John Schlipf, 541-737-6962

Faster method to spay cats found to be safe, effective

PORTLAND, Ore. – A new type of procedure to spay female cats has been shown to be safe, effective, and saves a little bit of time – which can be important in some high-volume programs such as those operated by animal shelters.

A study on the procedure has been published in the Journal of Feline Medicine and Surgery, by Kirk Miller, a clinical instructor with the College of Veterinary Medicine at Oregon State University, and practicing veterinarian with the Oregon Humane Society in Portland.

It found that a procedure called a “pedicle tie” is effective at stopping blood flow through two vessels that that go to a cat’s ovary, a preliminary step to removing the ovary and uterus. It’s essentially tying the vessels in a knot – and works just as well, and is about 30 percent faster, than a procedure used for decades that required multiple ligatures to accomplish the same purpose.

There had been no prior study on this approach, and some concern it might cause additional bleeding. But in a survey of 2,136 kittens and adult cats that were neutered using the new technique, it was found to safe with no significant increase in hemorrhagic complications, and slightly reduced the time the animal needed to be under anesthesia.

And, for an average procedure, it saves a couple of minutes out of an overall operation that can take from six to 20 minutes, depending on the skill and experience of the practitioner.

“Saving two minutes may not sound like much, but when you do thousands of these procedures every year, like we do, it can add up in savings of both time and money,” Miller said. “Over the course of a year this may free up about two weeks of time for both the surgeon and anesthetist. That increased efficiency means we can serve more animals, provide the care they need and make them eligible to find new homes.”

The procedure can be taught fairly easily and expertise in it gained within a week or two, Miller said. With its safety and efficacy now verified, it’s anticipated that the procedure may soon be used much more broadly, he said.

Aggressive spay and neuter programs are needed to help address broader concerns about unwanted and homeless companion animals. The American Society for Prevention to Cruelty to Animals estimates there may be as many as 70 million stray cats in the United States. Neutering of dogs and cats helps to address this critical problem, while improving both their behavior and their health.

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Unwanted impact of antibiotics broader, more complex than previously known

CORVALLIS, Ore. – Researchers at Oregon State University have discovered that antibiotics have an impact on the microorganisms that live in an animal’s gut that’s more broad and complex than previously known.

The findings help to better explain some of the damage these medications can do, and set the stage for new ways to study and offset those impacts.

The work was published online in the journal Gut, in research supported by Oregon State University, the Medical Research Foundation of Oregon and the National Institutes of Health.

Researchers have known for some time that antibiotics can have unwanted side effects, especially in disrupting the natural and beneficial microbiota of the gastrointestinal system. But the new study helps explain in much more detail why that is happening, and also suggests that powerful, long-term antibiotic use can have even more far-reaching effects.

Scientists now suspect that antibiotic use, and especially overuse, can have unwanted effects on everything from the immune system to glucose metabolism, food absorption, obesity, stress and behavior.

The issues are rising in importance, since 40 percent of all adults and 70 percent of all children take one or more antibiotics every year, not to mention their use in billions of food animals. Although when used properly antibiotics can help treat life-threatening bacterial infections, more than 10 percent of people who receive the medications can suffer from adverse side effects.

“Just in the past decade a whole new universe has opened up about the far-reaching effects of antibiotic use, and now we’re exploring it,” said Andrey Morgun, an assistant professor in the OSU College of Pharmacy. “The study of microbiota is just exploding. Nothing we find would surprise me at this point.”

This research used a “cocktail” of four antibiotics frequently given to laboratory animals, and studied the impacts.

“Prior to this most people thought antibiotics only depleted microbiota and diminished several important immune functions that take place in the gut,” Morgun said. “Actually that’s only about one-third of the picture. They also kill intestinal epithelium. Destruction of the intestinal epithelium is important because this is the site of nutrient absorption, part of our immune system and it has other biological functions that play a role in human health.”

The research also found that antibiotics and antibiotic-resistant microbes caused significant changes in mitochondrial function, which in turn can lead to more epithelial cell death. That antibiotics have special impacts on the mitochondria of cells is both important and interesting, said Morgun, who was a co-leader of this study with Dr. Natalia Shulzhenko, a researcher in the OSU College of Veterinary Medicine who has an M.D. from Kharkiv Medical University.

Mitochondria plays a major role in cell signaling, growth and energy production, and for good health they need to function properly.

But the relationship of antibiotics to mitochondria may go back a long way. In evolution, mitochondria descended from bacteria, which were some of the earliest life forms, and different bacteria competed with each other for survival. That an antibiotic would still selectively attack the portion of a cell that most closely resembles bacteria may be a throwback to that ingrained sense of competition and the very evolution of life.

Morgun and Schulzhenko’s research group also found that one of the genes affected by antibiotic treatment is critical to the communication between the host and microbe.

“When the host microbe communication system gets out of balance it can lead to a chain of seemingly unrelated problems,” Morgun said.

Digestive dysfunction is near the top of the list, with antibiotic use linked to such issues as diarrhea and ulcerative colitis. But new research is also finding links to obesity, food absorption, depression, immune function, sepsis, allergies and asthma.

This research also developed a new bioinformatics approach named “transkingdom network interrogation” to studying microbiota, which could help further speed the study of any alterations of host microbiota interactions and antibiotic impact. This could aid the search for new probiotics to help offset antibiotic effects, and conceivably lead to systems that would diagnose a person’s microbiome, identify deficiencies and then address them in a precise and individual way. 

Healthy microbiota may also be another way to address growing problems with antibiotic resistance, Morgun said. Instead of trying to kill the “bad” bacteria causing an illness, a healthy and functioning microbiota may be able to outcompete the unwanted microbes and improve immune function.

Collaborators on this research were from the OSU College of Pharmacy; OSU College of Veterinary Medicine; OSU College of Science; the National Cancer Institute; University of British Columbia; University of Maryland School of Medicine; and the National Institutes of Health.

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Andrey Morgun, 541-737-8047

Deworming programs in animal, human populations may have unwanted impacts

CORVALLIS, Ore. – A study of the effects of worming medications on infectious disease in wildlife herds showed an unexpected and alarming result – although it helped reduce individual deaths from a bovine tuberculosis infection, it hugely increased the potential for spread of the disease to other animals.

The findings, from one of the first field studies ever done on this issue, will be published Friday in the journal Science.

They were contrary to expectations based on laboratory studies, and suggest the possibility that broad use of medical treatments such as this can backfire. They may actually increase the problem with diseases they were meant to reduce.

Both in animals and possibly human disease, treatments that aid an individual could come at the expense of a wider spread of disease in the larger community, the research suggested.

“This study indicates that we need to better understand how some medical treatments affect other health issues, in particular infectious disease,” said Anna Jolles, an epidemiologist at Oregon State University and co-author of the study, along with Vanessa Ezenwa at the University of Georgia.

The research, supported by the National Science Foundation, was done with more than 200 animals in two herds of free-ranging African buffalo in Kruger National Park in South Africa. Half were given deworming medication and the others not.

It was known that infection with parasitic helminth worms can decrease the effective immune response against some infectious diseases, in this case bovine tuberculosis, which is common among these animals. Scientists expected the worming medications to save lives while reducing the risk of infection and disease progression.

They found that deworming treatments did improve the survival of animals infected with bovine tuberculosis – in fact, dewormed animals with tuberculosis survived just as well as TB-free animals. However, deworming did not reduce the risk of new infections, and there was a dramatic eight-fold increase in the number of buffalos that an infected animal could potentially infect – a reference to the “R-nought,” or reproductive multiplier that epidemiologists use to predict the potential for spread of infection in a community.

A buffalo with bovine tuberculosis but no worm treatments has, on average, the potential to infect about one other buffalo. This study found that after worm treatment, a buffalo with this disease had the theoretical potential to infect nine other buffalos. This difference was based on the finding that dewormed buffalo with TB can survive for years, whereas the life expectancy of untreated TB-infected buffalo was much shorter.

These issues are of significant concern not just for animal, but also human health, researchers say.

Helminth worm infections are among the most ubiquitous parasites on Earth, infecting 1 billion people and causing significant losses among both livestock and wildlife. Other studies have linked co-infection with these worms to increased risk of death from both tuberculosis and HIV/AIDS in human patients, largely due to their ability to reduce and otherwise skew the natural immune response to both viral and bacterial infection.

This is a larger problem in the developing world, and some major deworming programs in human populations are already in place due to the range of health concerns posed by the parasites. It’s believed that mass deworming programs may reduce overall deaths from some of the major killers in such areas, such as malaria, tuberculosis and HIV infection.

“These results are pretty alarming,” said Jolles, who is a researcher in both the OSU College of Science and College of Veterinary Medicine.

“We expected deworming effects to be all positive, both for individual buffalo, and in terms of reducing disease spread,” Jolles said. “But what we found is positive effects for individual animals, but potentially much faster disease spread at the population level.”

From these results in buffalo, Jolles said, one should not to jump to conclusions about changing deworming treatments in people. But they do raise questions about large, broad-based public deworming programs.

“We must pay attention to health problems that may increase as a result of the program, as well as problems that we are solving,” she said.

The findings also raise questions about aspects of animal agriculture, Jolles said, especially in developing countries. It may be important to match deworming programs with vaccines for infectious disease and other treatments to ensure that the overall health of the herd is protected.

The potential to actually increase spread of a disease following a health treatment such as deworming may vary widely, Jolles said, with different animal species and different infectious diseases.

More studies are urgently needed to address the primary question raised by this research, the scientists said. On a community level, will large-scale deworming treatments alleviate, or will they exacerbate the health impacts of other, sometimes deadly infections?

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Anna Jolles, 541-737-4719

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African buffalo

African buffalo