In Search of Kryptonite for Superbugs

Germs' ability to fight back when we try to kill them is creating increasing problems globally—so much so that the World Health Organization calls "antimicrobial resistance" (AMR) one of the top 10 public health threats.

Simply put, AMR develops when a bacterium encounters an antibiotic drug or cleaning agent that knocks it back but doesn’t wipe it out. Surviving organisms often have some natural resistance, and when they multiply, they’re harder to kill than ever. This unintentional selective breeding 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)

This week is World Antimicrobial Resistance Awareness Week; to mark it, we’re looking at how five University of Maryland researchers are …

Targeting Bacteria the Way Viruses Do
Nature itself knows how to keep bacteria in check. Veterinary medicine Professor Daniel Nelson focuses on replicating virus mechanisms to kill harmful bacteria in order to reduce the need for antibiotic drugs. The viruses he works with are harmless to humans and infect only specific bacteria, but they produce powerful enzymes—called endolysins—that kill their target’s cells by breaking down the cell walls. Nelson is developing ways to use them in vaccines and therapeutics against a host of human and animal diseases—and to kill a common soil microbe that slows fermentation in biofuel reactors. “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,” he said.

Fighting Bacteria With Their Own Weapons
Veterinary medicine Assistant Professor Seth Dickey has discovered a new class of antimicrobial peptides—tiny proteins—that bacteria secrete to compete. The peptides create large holes in the cell membranes of rival bacteria, killing them quickly.

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.

“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.”

Developing Natural Antimicrobials
Food and nutrition science Assistant Professor Ryan Blaustein 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.

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.

“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,” he said.

Shutting Down Pathways for Pathogens
Professor Debabrata Biswas from the Department of Animal and Avian Sciences and the Center for Food Safety and Security Systems 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
Veterinary medicine Assistant Professor Mostafa Ghanem 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.

Although sometimes antibiotic use is unavoidable, Ghanem emphasizes AMR education among farmers and industry stakeholders in order to preserve the effectiveness of antibiotics; with veterinarians, he recommends protecting the efficacy of antibiotics that are medically critical for humans by choosing other, non-medically important ones for animals.

“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.”