UMD Researchers Combat Antimicrobial Resistance in Human Health, Agriculture and Industry

To Mark World AMR Awareness Week, we feature five AMR-fighting faculty members

Image Credit: Emily Brown, Creative Commons

November 18, 2024 Kimbra Cutlip

Antimicrobial resistance (AMR) is on the rise globally, with resistant pathogens popping up throughout the food chain, from the soil crops are grown in to the facilities where meats are processed and the grocers we buy from. The World Health Organization calls AMR one of the top 10 threats to public health. It is a true one-health issue that ties together the welfare of people, animals and the environment.

Simply put, AMR develops when a bacterium encounters an antibiotic drug or cleaning agent that knocks it back but doesn’t kill all the bacterial cells. Those that survive have some natural resistance, and when they multiply, they come back stronger and harder to kill with those same chemicals. This unintentional selective breeding has led to the emergence of superbugs like Methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis and resistant strains of Salmonella and Escherichia coli (E. coli).

Combating AMR can feel like playing a game of whack-a-mole where the mole keeps getting bigger and harder to kill with every new appearance. But from a purely scientific perspective, AMR is a natural process that occurs everywhere bacteria exist. It is just a bacterium’s immune system fighting off an attack and improving with every generation. So, to win the game of whack-a-mole, or at least keep it from spiraling out of control, scientists are trying to understand how bacterial immune systems work, and what conditions in the environment can either aid their spread or keep them in check.

To mark World Antimicrobial Resistance Awareness Week, we’re featuring the work of five faculty members who are doing just that:

Understanding Bacteria and Using Their Biology Against Them

Daniel Nelson, a professor of veterinary medicine, capitalizes on the biology that naturally keeps bacteria in check. His work focuses on understanding, and replicating the mechanisms that viruses use to kill harmful bacteria. The viruses are harmless to humans and only infect specific bacteria, but they produce powerful enzymes—called endolysins—that kill their target’s cells by breaking down the cell walls. Nelson identifies these endolysins and is developing ways to use them in vaccines and therapeutics against a host of diseases like bacterial pneumonia, C. difficile, staph infections, Streptococcus mutans, which causes cavities, bovine mastitis, and equine strangles disease, to name just a few.

He is even working to develop endolysins that will kill a common soil microbe that slows down fermentation in biofuel reactors. Nelson and his team are engineering yeast to secrete the endolysin, helping to improve fermentation and increase ethanol production.

“Endolysins research is really like the poster child for one health,” Nelson said. “It’s mostly been studied for use in human health, but it can be applied in any arena where these natural processes are taking place and having an impact.”

Seth Dickey, an assistant professor of veterinary medicine, has discovered a new class of antimicrobial peptides, very small proteins or bits of protein, that bacteria secrete to compete with one another. These peptides create large holes in the cell membranes of rival bacteria, allowing the cell’s contents to spill out and killing them quickly. Although a bacterium’s own cells aren’t affected by the antimicrobial peptides they secrete, other antibiotic-resistant bacteria seem to have little resistance to them.

Dickey plans to figure out how these peptides form holes in cells and to identify the genetic code for producing these powerful bits of protein. That information may one day enable him to produce them in the laboratory at scale for use in therapeutics.

He is also investigating how genes in MRSA bacteria work together. By disrupting different combinations of genes with CRISPR technology, Dickey hopes to identify promising combinations of targets for drug therapies.

“There are still a lot of genes in MRSA that we don’t know the function of,” Dickey said, “and by learning how these genes, and the proteins they produce, interact with one another we may learn how to interrupt the critical functions they contribute to, such as how cells divide or build cell walls.”

Understanding the Environment and Developing Natural Antimicrobials

Ryan Blaustein, an assistant professor of nutrition and food science, is studying the genomes of bacteria found in soil and water to learn what genes could be responsible for antimicrobial resistance, and then identifying how those genes move through the agricultural system into the food supply. Part of that work involves trying to understand how microbial communities interact to facilitate or prevent resistance from spreading.

In a recent study, Blaustein found that adding manure and compost to soil boosted the total bacteria levels, but reduced the proportions of those that were antibiotic-resistant. He also found a correlation between pH levels in soil and tetracycline resistant bacteria, suggesting that pH management could offer one way of controlling some forms of AMR.

“We have an increasing sense of our connection to our microbiome,” Blaustein said, “and one of the things we’re doing is trying to promote healthier microbial diversity to see if we can keep the good players in our system and not select for things that could be problematic.”

Debabrata Biswas, professor of animal and avian sciences, is developing alternatives to antibiotics to prevent diseases and increase growth in poultry. By feeding chickens a formula of probiotics and plant-derived antioxidants known as phenolics, Biswas has found that he can change their gut microbiome so the animals are better able to fight infections and gain weight at the same time.

He is also investigating the environmental conditions that help certain types of microbes like Salmonella, which sickens people, and the Avibacterium, which affects chickens, persist in the food system.

“There are so many microbes in these environments, and some of these non-pathogenic species create pathways for pathogens to persist,” Biswas said. “One of the most important things to know is where these persistent infectious agents are coming from and how the environment is supporting them.” 

A Comprehensive Approach

Mostafa Ghanem, assistant professor of veterinary medicine, uses advanced molecular diagnostic and genotyping techniques to monitor the spread of poultry diseases and to develop vaccines against common bacteria. Ghanem is also studying how microbes in the respiratory tracts of chickens help them fend off infections with the goal of learning how beneficial microbes might be used to reduce the need for antibiotics.

By reducing the need for antibiotics in agriculture, Ghanem hopes to slow the emergence and spread of antibiotic-resistant bacteria. But sometimes antibiotic use is unavoidable, and as a researcher who is heavily involved in Extension, Ghanem emphasizes AMR education among farmers and industry stakeholders. He urges veterinarians to help preserve the effectiveness of antibiotics that are medically critical for humans by choosing other, non-medically important ones.

“We advocate for responsible, judicious antibiotic practices in agriculture,” Ghanem said. “And by advancing vaccines and microbiome research, we’re taking a multifaceted approach that broadens the mission of combating antimicrobial resistance."