Researchers Identify New Target To Fight Antibiotic Resistance
Heidi Opdyke
- Associate Dean of Marketing and Communications, MCS
- Email opdyke@andrew.cmu.edu
- Phone 412-268-9982
Antibiotic resistance is a growing global health crisis that makes common infections harder to treat and puts many medical procedures at risk. Now, Carnegie Mellon University researchers have uncovered a vulnerability in bacteria that could pave the way for an entirely new class of treatments.
The discovery, published today in Nature Communications, doesn’t kill the bacteria — a tactic that often leaves behind resistant survivors — but targets a key mechanism that controls bacterial behavior.
Drew Bridges, an assistant professor in Carnegie Mellon University’s Mellon College of Science, said the research could be an important tool in fighting a growing threat.
“Traditional antibiotics work in a simple way — they kill bacteria,” Bridges said. “It's the same problem as with chemotherapy — the survivors cause problems. When you apply a bunch of antibiotics, a subpopulation of cells survives, they repopulate the population, and they're all resistant.”
Bacteria are smarter than people think
Bacteria behavior is central to Bridges’ work. He said that people might think of bacteria as the simple organisms described in the pages of high school biology books. But bacteria are far more sophisticated — they take action, communicate and strategize for survival.
“We want to know if we can alter the actions that make bacteria infectious,” Bridges said. “Bacteria create biofilms that help them spread, stick to cells or swim into tissues. If we can shift those behaviors, maybe we can treat or prevent infections in a new way.”
Bridges and graduate student Emmy Nguyen found a way to change behavior in Vibrio cholerae, the bacteria that causes cholera. They identified a pathway that regulates biofilm — sticky communities where bacteria can survive and thrive.
“Thanks in part to biofilms, bacteria can grow in nearly every environment,” Bridges said. “If we can understand how that fundamental mechanism works, we could target that pathway to tip them into a weakened, less infectious state.”
The study illuminated more about bacterial behavior, Nguyen added.
“What makes this study so exciting is that this pathway doesn’t just control biofilms — it also regulates a wide range of bacterial responses, including metabolism, movement and stress defenses,” Nguyen said. “We think that when V. cholerae is in a hostile environment, activating this pathway helps it prioritize protection over proliferation.”
Not just cholera
Cholera is a problem for many parts of the world without access to clean drinking water, and V. cholerae is an important model organism for studying infectious diseases. But Nguyen said it can be difficult to study infection because species differ so much from one another — the basic processes that drive the biofilm lifecycle may be different from those in other disease-causing microbes.
To determine if the pathway that controls the biofilm lifecycle in V. cholerae was found in other bacteria, Bridges and Nguyen turned to M. R. Pratyush, a graduate student working with Associate Professor of Biological Sciences N. Luisa Hiller. Pratyush completed a bioinformatic analysis and gave the team some good news — it is.
“The protein that V. cholerae uses to control biofilm growth is also found in many other kinds of bacteria,” he explained. “What’s interesting is that this biofilm protein belongs to a module composed of multiple proteins, and the whole module is found in many other bacteria. This means the way these proteins work together may be similar across many different species.”
For Bridges and Nguyen, this information opened the door to explore how this shared mechanism might be used to control bacterial behaviors or lifestyle decisions.
From fundamental science to future solutions
The researchers teamed up with colleagues at the University of Pittsburgh to study how protein interaction within the pathway can influence bacterial lifestyle decisions. Then, working with scientists at Tufts University School of Medicine, they tested whether this pathway plays a role in infection.
At Tufts, the team compared normal bacteria (wild type) with versions that had the pathway activated (mutant). When they infected mice with these strains, they found that the mutant bacteria struggled to grow and colonize the host.
“Our goal is to activate this pathway and weaken the bacteria. To do that, we’re searching for small molecules that can turn the pathway on,” Nguyen explained.
Looking ahead, the Bridges Lab plans to build on these discoveries to design new types of treatments.
“We’ve always been a basic science lab, focused on understanding how bacteria work,” Bridges said. “But more and more, we’re thinking about how to translate that knowledge. Antibiotic resistance is a crisis, and developing new kinds of therapeutics that work differently is the direction we’re headed,” he said.
