A research team at Indiana University Bloomington has identified a chemical approach to address the growing problem of antibiotic resistance. The study, led by assistant professor J.P. Gerdt in the College of Arts and Sciences, focuses on weakening bacterial defenses against viruses.
“I love thinking outside the box when it comes to the antibiotic resistance problem,” said Gerdt.
Antimicrobial resistance, where bacteria and fungi become immune to drugs designed to kill them, is considered a major public health threat by the Centers for Disease Control and Prevention. To address this, Gerdt’s lab studies how bacterial immune systems work in order to find ways to inhibit them.
“Bacteria get sick, too,” Gerdt said. “Our lab tries to understand how their immune systems work so we can figure out how to inhibit them.”
The research explores bacteriophages—viruses that attack bacteria—as an alternative to antibiotics. Unlike antibiotics, which can destroy both harmful and beneficial bacteria, bacteriophages target specific strains.
However, bacteria can also develop immunity against these viruses. Former lab member Zhiyu Zang, now at the Swiss Federal Technology Institute of Lausanne, discovered a chemical molecule that helps bacteriophages bypass bacterial defenses when used together.
This discovery was detailed in Zang and Gerdt’s paper “Chemical inhibition of a bacterial immune system,” published in Cell Host and Microbe.
While antibiotics remain central in treating human infections, this new approach could be relevant for difficult-to-treat cases and applications such as agriculture where overuse of antibiotics contributes to resistance.
Gerdt’s team began by studying a bacterium suitable for undergraduate research. Students like Olivia Duncan contributed by helping identify molecules that could suppress the bacterium’s immune response.
“Our study is important not just because we found the first example of a small molecule that can inhibit a bacteria’s immune system,” Zang said. “It’s also important because the immune system we’re studying in this paper is present in around 2,000 different bacteria species.”
The findings may help develop strategies against pathogenic bacteria such as Pseudomonas aeruginosa or Staphylococcus aureus—both known for hospital-acquired infections resistant to treatment.
Duncan and Zang screened commercial compound libraries until they found one molecule capable of assisting viruses in evading bacterial immunity.
“Our goal is to have a collection of inhibitors that will work for different immune systems,” Gerdt said. “We hope that this paper will be a catalyst for other labs to work on this with us as a community. That’s what makes this paper so exciting: We’re starting something new and seeing where it takes off.”
Duncan described her experience in the lab as one shaped by curiosity fostered by Gerdt: “J.P. is open to where the science takes him.” She noted his encouragement for researchers to engage actively with questions during meetings.
Gerdt added: “I get excited trying to think about the non-obvious way to solve these problems. Is our solution simple enough to be adopted widespread? I’m not sure yet, but it’s the process of thinking outside the box and seeing those alternative strategies work that’s thrilling.”
Indiana University Bloomington serves as Indiana University’s main campus and operates as a public research university with an emphasis on advancing research and innovation while welcoming students from all 50 states and more than 150 countries (https://bloomington.iu.edu/). The university maintains historic limestone architecture on its campus and contributes significantly to Indiana’s economy and cultural life (https://bloomington.iu.edu/).
