by Marcia Hill Gossard ’99, ‘04

Doug-Call-and-Beatus-Lyimo
Dr. Douglas Call (left) with Beatus Lyimo, a graduate student at the Nelson Mandela African Institution for Science and Technology. They are working in the lab at the Mandela Institution where Dr. Call and his team process samples to analyze for antibiotic resistance.

Bacteria can do something remarkable. They can share genes. So, if one bacterium is resistant to a particular antibiotic, such as tetracycline, it can pass that resistant gene to another bacterium. That bacterium will become resistant and can pass its resistant gene to another bacterium. And they can keep the resistance for a long time, which allows antibiotic resistance to spread widely.

This highly adaptable behavior, while good for bacterial survival, poses a major risk to human health. Treatments for common infections are becoming ineffective in some parts of the world according to a recent report by the World Health Organization. Globally there are already very high rates of antibiotic resistance for urinary tract infections and pneumonia.

Standard recommendations to reduce antibiotic resistance include using antibiotics only when medically necessary. The FDA recently released guidelines to discontinue the use of antibiotics in food animals who are not showing signs of illness. U.S. prescription guidelines for people are created to help ensure antibiotics are only prescribed when someone has a bacterial infection, not a viral illness. Both will have some impact. But according to researchers at the Paul G. Allen School for Global Animal Health, it is unlikely to do enough.

“Treatment guidelines in the United States alone are not sufficient to solve the problem,” said Guy Palmer, director of the Paul G. Allen School for Global Animal Health.

In many parts of the world, antibiotics are sold over the counter or the quality of the antibiotics is not well regulated, said Palmer. And because the spread of resistant bacteria is accelerated by travel and transporting food, or by more people moving into urban areas—particularly those with poor sanitation—the problem is much more complicated.

“The movement of people and food makes it a global issue,” said Palmer.

Because antibiotic resistance is a complex problem, scientists at the Allen School are taking several approaches to understand the emergence and spread of antibiotic resistance. Researchers are looking at the transmission of resistant bacteria (how it spreads from animals to animals or animals to humans), and how bacteria maintain their resistance to antibiotics. They are also identifying reservoirs, such as untreated water or soil, that can harbor resistant bacteria. Many reservoirs also provide ways for bacteria to travel.

“Untreated water is also a means of transmission,” said Palmer. “We want to learn what the transmission pathways are and how they can be decreased.”

Dr. Douglas Call, professor in the Allen School, is currently conducting research in east Africa with the Nelson Mandela Institution in Arusha, Tanzania, to better understand how resistant bacteria move between animals and between humans and animals. Tanzania provides an ideal setting for understanding how resistant bacteria travel. Locally raised domestic livestock, people, and wildlife live close together, which offers a unique research opportunity, said Call. People routinely come in contact with animals, share water, transport animals, and prepare food—all things that can spread resistant strains of bacteria. Because the problem is truly global, resistant bacteria found in east Africa can travel across the world.

From this research Dr. Call and his team hope to better understand the proportion of resistant bacteria from people misusing antibiotics, from antibiotic use for infections in livestock, and from local and global transportation. Knowing how resistant bacteria moves across the landscape can help inform policy decisions to control the emergence and spread of antibiotic resistance.

Dr. Call and his team have preliminary data suggesting that dogs living in Maasai bomas (houses) are a reservoir for resistant bacteria. They may have 70 to 90% resistant bacteria, said Call. Those bacteria can then be transmitted to other animals or humans. “Dogs may be the signal for resistance coming into an E. coli population in humans,” said Call.

“Improved surveillance is needed to better understand which policies might be the most effective for reducing antibiotic resistance,” said Call. Without this knowledge, he says it is difficult to decide which polices to use or to even know if the ones that have been chosen will really lower resistance.

Rather than waiting for the number of resistant bacteria to decline, which happens gradually after antibiotic overuse or misuse stops, Dr. Call is directing part of his research to actively drive down the number of resistant bacteria in reservoirs. If his work is successful, then the number of resistant bacteria may reduce much faster than by just discontinuing use alone.

Murugan Subbiah and Beatus Lyimo
Murugan Subbiah (left), a post-doctoral student in Dr. Call’s lab, with graduate student Beatus Lyimo, from the Nelson Mandela African Institution for Science and Technology. Dr. Subbiah is spearheading the sample processing effort at the Tanzanian lab.

“Driving the equilibrium is something we   want to do actively,” said Call. “Most resistance traits don’t go away when we stop using antibiotics. But with active selection against resistant bacteria we should be able to speed the process until resistance drops below a clinically important level.”

Improving health practices, such as vaccinations for people and animals, can also help reduce the number of illnesses that ultimately would need to be treated with antibiotics. Scientists at the Allen School are working on disease prevention by discovering ways to reduce the spread of zoonotic diseases, such as brucellosis, Salmonella, and Q fever that affect human and livestock health. They are also learning how livestock-dependent families fare when animals receive vaccinations or improved treatment options for diseases such as East Coast fever, which is a major cause of calf deaths among East African indigenous cattle.

The transmission of resistant bacteria or the number of reservoirs can be changed, says Palmer. Through their research they expect to find ways to mitigate transmission pathways and reduced the number of reservoirs.

“Resistance from antibiotic use is inevitable,” said Palmer. “But the consequences and rate of spread are not inevitable. We can minimize the spread and emergence of resistance.”

For more information about the antibiotic resistance program at the Allen School.