Cleaning up a breeding ground for antimicrobial resistance

BUFFALO, N.Y. — Around the world, bacteria and viruses are developing resistance to the drugs used to treat them, creating one of the greatest global health challenges of our time.

To fight this problem, an international research team is targeting an oft-overlooked haven where drug-resistant “superbugs” may thrive: wastewater treatment plants.

Inside these facilities, communities of bacteria dwell in sewage sludge that’s waiting to be treated. This muddy soup is often also rich in antibiotics and other medicines, a combination that may lead to a “survival of the fittest” situation where drug-resistant bacteria prosper while nonresistant strains die out, says Diana Aga, a chemistry professor in the University at Buffalo’s College of Arts and Sciences.

Aga, an environmental chemist, is part of a team of scientists and engineers that has been awarded a $3.6 million Partnerships for International Research and Education (PIRE) grant by the National Science Foundation (NSF) to explore how to improve wastewater treatment to prevent the proliferation of superbugs.

“Antibiotic resistance is a global problem, and a lot of researchers are trying to fight it by creating new drugs,” Aga says. “We are looking at the problem from a different angle: We are trying to prevent its spread.”

The new NSF study is led by Peter Vikesland, professor of civil and environmental engineering at Virginia Tech, with collaboration from UB and two other U.S. universities, as well as international partners including six universities in Asia and four in Europe. UB’s portion of the NSF grant is $530,800.

The global team is appropriate given the international nature of the problem and its scale: The Centers for Disease Control and Prevention estimates that at least 23,000 people are killed by drug-resistant infections in the U.S. alone each year, and the World Health Organization has identified such infections as an increasingly serious threat to global public health that requires action across all government sectors and society.

Inside the holding tanks of wastewater treatment plants, bacteria are exposed constantly to antibiotics that enter the sewers when people taking the drugs expel them. Under these conditions, “some bacteria develop resistance genes that help them survive or resist the antimicrobials by either deactivating the drugs or eliminating them from the cell,” Aga says.

Nonresistant bacteria in the sludge may also acquire resistance genes from other microbes through a process of DNA exchange called horizontal gene transfer.

Since wastewater treatment plants have historically focused on removing organic matter and nutrients such as nitrogen and phosphorus from wastewater, chemicals such as pharmaceuticals were largely ignored until recent years, when scientists and public health officials started to recognize the danger they posed, Aga says.

Yet despite recent advancements, water released from wastewater treatment plants often contains significant amounts of antimicrobial drugs, resistant organisms and resistance genes. Once in the environment, these elements enter rivers and streams, and may potentially contaminate food crops when biosolids are applied as fertilizer, or when recycled water is used for irrigation, Aga said.

In the new study, the research team will first take stock of wastewater treatment practices in diverse locations around the world, from Switzerland, which has extremely advanced treatment systems, to India, where treatment of sewage is often minimal and sometimes nonexistent. The project will work in countries like the U.S., where antibiotics must be prescribed, and countries like the Philippines, where the drugs are available over the counter.

The scientists will measure levels of antibiotics, antimicrobial-resistant organisms and resistance genes in both untreated sludge and in treated water released from plants. Aga’s lab will be key to this effort, which will help the scientists understand the scope of the problem they’re facing. Her research group at UB has developed highly sensitive analytical methods that use state-of-the-art instrumentation to simultaneously measure multiple classes of antibiotics and the products they break down into in wastewater.

The team will study how treatment practices and the design of facilities influence the growth of resistance: For example, is it better to chlorinate wastewater seasonally, or more often? How does the amount of time that sludge spends in a holding tank influence resistance? What are the levels and the types of antibiotics present in wastewater that can enhance the emergence of antibiotic resistance and promote horizontal gene transfer in sludge?

Answers to these and other questions will guide the researchers as they develop and evaluate advanced treatment systems — such as those that use nanotechnology — as well as cost-sensitive wastewater treatment methods designed to mitigate the spread of antibiotics and antimicrobial resistance in the environment.

“The area we’re working in is one that has not been studied much,” says Aga, a member of RENEW (Research and Education in eNergy, Environment and Water), a Community of Excellence at UB that harnesses faculty strengths across disciplines to tackle complex environmental challenges. “We want to look at different wastewater treatment systems and practices around the world, identify what factors and conditions enhance the removal of antibiotics and resistance genes in wastewater, and figure out new and effective ways to control the spread of antibiotic resistance through discharges from wastewater treatment plants.”