Human antibiotic use threatens endangered wild chimpanzees

The number of chimpanzees in Gombe National Park, the site of Jane Goodall's groundbreaking field studies, are down to about 95. "By misusing antibiotics, people can actually harm not only themselves, but also the species they share an environment with," says Emory disease ecologist Thomas Gillespie.

By Carol Clark

It’s well established that infectious disease is the greatest threat to the endangered chimpanzees made famous by the field studies of Jane Goodall at Gombe National Park in Tanzania. Now, new research led by scientists at Emory University shows that nearly half of the fecal samples from wild chimpanzees contain bacteria that is resistant to a major class of antibiotics commonly used by people in the vicinity of the park. 

The journal Pathogens published the findings. 

“Our results suggest that antibiotic-resistant bacteria is actually spreading from people to non-human primates by making its way into the local watershed,” says Thomas Gillespie, senior author of the study and associate professor in Emory’s Department of Environmental Sciences and Rollins School of Public Health. “People are bathing and washing in the streams, contaminating the water with drug-resistant bacteria where wild chimpanzees and baboons drink.” 

The researchers tested for genes conferring resistance to sulfonamides — drugs often used by people in the region to treat diarrheal diseases — in fecal samples from humans, domestic animals, chimpanzees and baboons in and around Gombe National Park. They also tested stream water used by these groups. 

Sulfonamide resistance appeared in 74 percent of the human samples overall, 48 percent of chimpanzee samples, 34 percent of baboon samples, and 17 percent of the domestic animal samples. Sulfonamide also showed up in 19 percent of the samples taken from streams shared by people, domestic animals and wildlife. 

The researchers also tested all the groups in the study for genes conferring resistance to tetracycline — another class of antibiotics that is used much less frequently by people in the vicinity, likely due to its greater expense and the fact that it is less available in the area. As expected, very few of the fecal samples from any of the groups, and none of the water samples from the streams, showed evidence of tetracycline resistance. 

First author of the study is Michele Parsons, who did the work as an Emory doctoral student in Environmental Sciences. Parsons has since graduated and works at the Centers for Disease Control and Prevention (CDC). Co-authors include researchers from the Jane Goodall Institute, the CDC, the University of Minnesota and Franklin and Marshall College. 

Gillespie is a disease ecologist who helped pioneer the “One Health” approach to protect humans, ecosystems and biodiversity. His projects in Africa, including the collaboration with the Jane Goodall Institute in Tanzania, are focused on helping farmers subsisting amid fragmented forests co-exist with primates and other wildlife in ways that minimize the risk of pathogen exchange between species, known as “spillover.” The virus that causes AIDS, for example, spilled over from chimpanzees to people. 

“It’s important to consider both sides of the story — human health and well-being, as well as conservation of chimpanzees and other species,” Gillespie says. 

Human encroachment has taken a toll on the great apes, due to fragmented habitat and the exchange of pathogens. Today, the number of chimpanzees in Gombe National Park are down to about 95. 

Diarrheal diseases are common in the area and people often turn to cheap sulfonamide antibiotics that are available without a prescription at small stores that act as informal pharmacies, selling drugs, soap and other necessities. Wild chimpanzees also suffer from wasting diseases that can be related to bacterial and other enteric pathogens that affect their ability to maintain calorie intake and absorb nutrients. 

“The majority of people in our sampling harbored bacteria resistant to the sulfonamide medication they are taking,” Gillespie says. “In those cases, they’re spending their money on a drug that is not helping them get better. Overuse of such drugs creates the potential for more lethal, antibiotic-resistant ‘super bugs’ to emerge.” 

The research findings will now support the development of interventions. 

More guidance is needed locally regarding the proper use of antibiotics, Gillespie says. He adds that it is also important to improve hygiene for wash-related activities in area streams, as well as to improve disposal of human waste materials. 

“By misusing antibiotics, people can actually harm not only themselves, but also the species they share an environment with,” Gillespie says. “After drug-resistant bacteria jump into chimpanzees, it can further evolve with the chimpanzees and then spill back into humans. We need to be thinking about infectious diseases within evolutionary and ecological frameworks, something that’s not often done in medicine.” 

The study was funded by the Morris Animal Foundation, the Emory Global Health Institute, the Arcus Foundation, the Leo S. Guthman Foundation and the National Institutes of Health.

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Georgia Aquarium otters join list of animals testing positive for SARS-CoV-2

Otters are Mustelids, a diverse group of carnivorous mammals that includes mink and ferret — two other species that have also become infected with SARS-CoV-2. (Getty Images)

By Carol Clark

The recent positive SARS-CoV-2 tests of Asian small-clawed otters at the Georgia Aquarium add to the mystery of why some animals may be more susceptible than others to the virus that causes COVID-19. 

“In one sense, it’s not surprising to see otters infected, because we’ve already seen infections in mink and ferrets, which are closely related species,” says Thomas Gillespie, associate professor in Emory University’s Department of Environmental Sciences and Rollins School of Public Health. 

Otters, mink and ferrets are all Mustelids, a diverse group of carnivorous mammals, notes Gillespie, a disease ecologist who studies how pathogens jump between wildlife, domestic animals and people.

Most of the research into what animal species may be susceptible to SARS-CoV-2 is based on the genetics of protein binding sites that the virus uses to gain a foothold in a host. People, great apes and some monkeys have the highest susceptibility, according to this research, Gillespie says. 

In January, some members of the gorilla troop at the San Diego Zoo tested positive for SARS-CoV-2, after they exhibited COVID-19 symptoms. 

“What’s surprising,” Gillespie says, “is that Mustelids are at the opposite end of the spectrum in terms of a binding propensity with SARS-CoV-2. In one of the more robust studies to date, they fell into the lower range of binding scores among 400 species of vertebrates. And yet, they keep popping up with infections. That’s where the mystery lies.” 

The Georgia Aquarium announced in an April 18 news release that the otters were tested after showing symptoms such as sneezing, runny noses, lethargy and coughing. The animals were removed from their exhibit for behind-the-scenes care and are expected to make a full recovery, the release stated. 

The virus that causes COVID-19 is zoonotic, meaning that it originated in animals — most likely horseshoe bats — and may have passed through another species before making its way to humans. 

“It’s critical right now for the world to focus on preventing human-to-human transmission of the virus,” Gillespie says. “But it’s also important to consider the longer-term, bigger picture of how pathogens can spill over from animals to people and then back to animals again.” 

Gillespie helped pioneer the One Health approach to protecting humans, ecosystems and biodiversity. The primary risks for future spillover of zoonotic diseases are deforestation of tropical environments and large-scale industrial farming of animals, he says. 

In late 2020, COVID-19 outbreaks were seen in mink around the world, including the United States, at farms that mass-produce the animals for the fur trade. The mink are kept in densely packed conditions that are ideal for spreading pathogens, Gillespie says. 

Denmark culled 17 million mink after the virus spread from the human caretakers to the animals, then mutated and spread back to some of the human caretakers. 

“The good news is that there are relatively few documented cases of animal transmission to humans, and these appear to be restricted to the most ideal conditions for transmission, such as the crowded conditions of industrial mink farming,” Gillespie says. 

Ferrets are a common laboratory model for the study of respiratory diseases, due to their unique respiratory biology. Experimental studies have shown that they can easily be infected with SARS-CoV-2. 

The black-footed ferret is among the most endangered mammals in North America. That prompted researchers at the U.S. National Wildlife Health Center last December to start testing a veterinary vaccine for COVID-19 on a captive population of the animals at the National Black-footed Ferret Conservation Center in Colorado. 

Almost all of the species that have tested positive for SARS-CoV-2, including cats, dogs, tigers, gorillas and a few other mammals, live in close proximity to people — either as pets, in zoos or in laboratories. One exception is a wild mink, found near a mink farm in Utah, that tested positive for SARS-CoV-2, according to the U.S. Department of Agriculture. 

“Testing of wildlife is rare,” Gillespie says. “And most testing of captive animals is done only if they show symptoms, suggesting there may be many more asymptomatic cases. There are a lot of important questions into how SARS-CoV-2 may affect animals that we have not yet started exploring.” 

The questions are important to protect both the health of animals and people, he adds. 

“Widespread infection within a population of a novel virus is the kind of event that could potentially push endangered and critically endangered species over the edge,” Gillespie says. “And any time a virus enters a new species with different selective pressures, that provides more opportunities for new mutants of the virus to evolve and potentially spill over into humans.”

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Physicists develop theoretical model for neural activity of mouse brain

"One of the wonderful things about our model is that it's simple," says Mia Morrell, who did the research as an Emory senior majoring in physics. Morrell graduated last year and is now in New Mexico, above, where she is completing a post-baccalaureate physics program at Los Alamos National Laboratory.

By Carol Clark

The dynamics of the neural activity of a mouse brain behave in a peculiar, unexpected way that can be theoretically modeled without any fine tuning, suggests a new paper by physicists at Emory University. Physical Review Letters published the research, which adds to the evidence that theoretical physics frameworks may aid in the understanding of large-scale brain activity. 

“Our theoretical model agrees with previous experimental work on the brains of mice to a few percent accuracy — a degree which is highly unusual for living systems,” says Ilya Nemenman, Emory professor of physics and biology and senior author of the paper. 

The first author is Mia Morrell, who did the research for her honors thesis as an Emory senior majoring in physics. She graduated from Emory last year and is now in a post-baccalaureate physics program at Los Alamos National Laboratory in New Mexico. 

“One of the wonderful things about our model is that it’s simple,” says Morrell, who will start a Ph.D. program in physics at New York University in the fall. “A brain is really complex. So to distill neural activity to a simple model and find that the model can make predictions that so closely match experimental data is exciting.” 

The new model may have applications for studying and predicting a range of dynamical systems that have many components and have varying inputs over time, from the neural activity of a brain to the trading activity of a stock market. 

Co-author of the paper is Audrey Sederberg, a former post-doctoral fellow in Nemenman’s group, who is now on the faculty at the University of Minnesota. 

The work is based on a physics concept known as critical phenomena, used to explain phase transitions in physical systems, such as water changing from liquid to a gas. 

In liquid form, water molecules are strongly correlated to one another. In a solid, they are locked into a predictable pattern of identical crystals. In a gas phase, however, every molecule is moving about on its own. 

“At what is known as a critical point for a liquid, you cannot distinguish whether the material is liquid or vapor,” Nemenman explains. “The material is neither perfectly ordered nor disordered. It’s neither totally predictable nor totally unpredictable. A system at this ‘just right’ Goldilocks spot is said to be ‘critical.’” 

Very high temperature and pressure generate this critical point for water. And the structure of critical points is the same in many seemingly unrelated systems. For example, water transitioning into a gas and a magnet losing its magnetism as it is heated up are described by the same critical point, so the properties of these two transitions are similar. 

In order to actually observe a material at a critical point to study its structure, physicists must tightly control experiments, adjusting the parameters to within an extraordinarily precise range, a process known as fine-tuning. 

In recent decades, some scientists began thinking about the human brain as a critical system. Experiments suggest that brain activity lies in a Goldilocks spot — right at a critical transition point between perfect order and disorder. 

“The neurons of the brain don’t function just as one big unit, like an army marching together, but they are also not behaving like a crowd of people running in all different directions,” Nemenman says. “The hypothesis is that, as you increase the effective distance between neurons, the correlations between their activity are going to fall, but they will not fall to zero. The entire brain is coupled, acting like a big, interdependent machine, even while individual neurons vary in their activity.” 

Researchers began searching for actual signals of critical phenomena within brains. They explored a key question: What fine tunes the brain to reach criticality? 

In 2019, a team at Princeton University recorded neurons in the brain of a mouse as it was running in a virtual maze. They applied theoretical physics tools developed for non-living systems to the neural activity data from the mouse brain. Their results suggested that the neural activity exhibits critical correlations, allowing predictions about how different parts of the brain will correlate with one another over time and over effective distances within the brain. 

For the current paper, the Emory researchers wanted to test whether fine-tuning of particular parameters were necessary for the observation of criticality in the mouse brain experiments, or whether the critical correlations in the brain could be achieved simply through the process of it receiving external stimuli. The idea came from previous work that Nemenman’s group collaborated on, explaining how biological systems can exhibit Zipf’s law — a unique pattern of activity found in disparate systems. 

“We previously created a model that showed Zipf’s law in a biological system, and that model did not require fine tuning,” Nemenman says. “Zipf’s law is a particular form of criticality. For this paper, we wanted to make that model a bit more complicated, to see if could predict the specific critical correlations observed in the mouse experiments.” 

The model’s key ingredient is a set of a few hidden variables that modulate how likely individual neurons are to be active. 

Morrell wrote the computer code to run simulations and test the model on her home desktop computer. “The biggest challenge was to write the code in a way that would allow it to run fast even when simulating a large system with limited computer memory without a huge server,” she says. 

The model was able to closely reproduce the experimental results in the simulations. The model does not require the careful tuning of parameters, generating activity that is apparently critical by any measure over a wide range of parameter choices. 

“Our findings suggest that, if you do not view a brain as existing on its own, but you view it as a system receiving stimuli from the external world, then you can have critical behavior with no need for fine tuning,” Nemenman says. “It raises the question of whether something similar could apply to non-living physical systems. It makes us re-think the very notion of criticality, which is a fundamental concept in physics.” 

The computer code for the model is now available online, so that anyone with a laptop computer can access it and run the code to simulate a dynamic system with varying inputs over time. 

“The model we developed may apply beyond neuroscience, to any system in which widespread coupling to hidden variables is extant,” Nemenman says. “Data from many biological or social systems are likely to appear critical via the same mechanism, without fine-tuning.” 

The current paper was partially supported by grants from the National Institutes of Health and the National Science Foundation.

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Chemists develop tools that may help improve cancer diagnostics, therapeutics

A process known as methylation helps regulate on-and-off switches to keep a host of systems in the body functioning normally. "But the process can get hijacked, creating modifications that may lead to diseases," explains Ogonna Nwajiobi (above), an Emory Ph.D. student in chemistry and first author of the paper.

By Carol Clark

Chemists developed a method to detect changes in proteins that may signal the early stages of cancer, Alzheimer’s, diabetes and other major diseases. Angewandte Chemie published the work, led by chemists at Emory University and Auburn University. The results offer a novel strategy for studying links between unique protein modifications and various pathologies. 

“The knowledge we gain using our new, chemical method holds the potential to improve the ability to detect diseases such as lung cancer earlier, when treatment may be more effective,” says Monika Raj, senior author of the paper and Emory associate professor of chemistry. “A detailed understanding of protein modifications may also help guide personalized, targeted treatment for patients to improve a drug’s efficacy against cancer.” 

The researchers provided a proof of concept for using their method to detect single protein modifications, or monomethylation. Their lab experiments were conducted on the protein lysine expressed from E.coli and other non-human organisms. 

Lysine is one of the nine essential amino acids that is critical to life. After lysine is synthesized in the human body, changes to the protein, known as methylation, can occur. Methylation is a biochemical process that transfers one carbon atom and three hydrogen atoms from one substance to another. Such modifications can occur in single (monomethylation), double (dimethylation) or triple (trimethylation) forms. Demethylation reverses these modifications. 

The small tweaks of methylation and demethylation regulate biological on-off switches for a host of systems in the body, such as metabolism and DNA production. 

“In a normal state, the methylation process creates modifications that are needed to keep your body functioning and healthy,” says Ogonna Nwajiobi, an Emory Ph.D. student in chemistry and first author of the paper. “But the process can get hijacked, creating modifications that may lead to diseases.”

Modifications to lysine, in particular, he adds, have been linked to the development of many cancers and other diseases in humans. 

Sriram Mahesh, from Auburn University is co-first author of the paper. Xavier Streety, also from Auburn, is a co-author. 

The Raj lab, which specializes in developing organic chemistry tools to understand and solve problems in biology, wanted to devise a method to detect monomethylation marks to lysine that have been expressed by an organism. Monomethylation is especially challenging to detect since it leaves negligible changes in the bulk, charge or other characteristics of a lysine modification.

The researchers devised chemical probes, electron-rich diazonium ions, that couple only with monomethlyation sites at certain biocompatible conditions that they can control, including a particular pH level and electron density. They used mass spectroscopy and nuclear magnetic resonance techniques to show that they had selectively hit the correct targets, and to confirm the coupling of atoms at the sites. 

The method is unique because it directly targets the monomethylation sites. Another unique feature of the method is that it is reversible under acidic conditions, allowing the researchers to uncouple the atoms and regenerate the original state of a monomethylation site. 

The Raj lab now plans to collaborate with researchers at Emory’s Winship Cancer Institute to test the new method on tissue samples taken from lung cancer patients. The goal is to home in on differences in lysine monomethylation sites of people with and without lung cancer. 

“It’s like a fishing expedition,” Nwajiobi explains. “The first step is to use our method to find the lysine monomethylation sites in tissue samples, which is difficult to do because of their low abundance. Once we’ve found the sites, our method then allows us to reverse the coupling with our chemical probe, so the functions of the sites can be studied in their intact, original forms.” 

Practical methods for early detection of many diseases, like lung cancer, are needed to help improve patient outcomes. “If we can develop more ways to identify lung cancer earlier, that may open the door for treatments that greatly improve the survival rate,” Raj says. 

The researchers hope to study lysine monomethylation differences between samples taken from patients at different stages of lung cancer, between patients with or without a family history of the disease, and between those who have smoked and those who have not. Knowledge gained from such analyses could set the stage for more personalized, targeted treatments, Raj says. 

Her lab is also developing chemical tools to selectively detect lysine dimethylation and trimethylation sites, in order to help more fully characterize the role of lysine methylation in disease. 

“We hope that other researchers will also apply our methods, and the chemical tools we are developing, to better understand a range of cancers and many other diseases associated with lysine methylation,” Raj says. 

The work was funded by the National Science Foundation.

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