Antibiotic resistance is an escalating global health threat, making common infections harder to treat and jeopardizing many medical procedures. Researchers at Carnegie Mellon University have identified a bacterial vulnerability that could lead to a new class of therapies. Rather than killing bacteria—which often leaves behind resistant strains—the approach targets a key mechanism that regulates bacterial behavior. The study is published in Nature Communications. Drew Bridges, assistant professor at Carnegie Mellon’s Mellon College of Science, noted that this research could provide a valuable tool in combating the rising threat of antibiotic resistance.

“Traditional antibiotics operate by killing bacteria,” Bridges explained. “The problem is similar to chemotherapy—surviving cells can create issues. When antibiotics are applied, a subpopulation of bacteria survives, repopulates, and becomes resistant.”

Figure 1. Modulating Bacterial “Decisions” to Fight Resistance

The Surprising Intelligence of Bacteria

Bacterial behavior is at the core of Bridges’ research. While often viewed as simple organisms in high school biology, bacteria are far more sophisticated, capable of communication, strategic action, and survival tactics. “We want to see if we can alter the behaviors that make bacteria infectious,” Bridges explained. “Bacteria form biofilms to spread, adhere to cells, or move into tissues. By modulating these behaviors, we may be able to treat or prevent infections in entirely new ways.” Figure 1 shows Modulating Bacterial “Decisions” to Fight Resistance.

Bridges and graduate student Emmy Nguyen discovered a way to modify the behavior of Vibrio cholerae, the bacterium responsible for cholera, by identifying a pathway that regulates biofilms—sticky bacterial communities that promote survival. “Biofilms allow bacteria to thrive in nearly any environment,” Bridges explained. “By understanding this fundamental mechanism, we could target the pathway to push bacteria into a weakened, less infectious state.” Nguyen added, “This pathway doesn’t just control biofilms—it also influences metabolism, movement, and stress responses. In hostile environments, activating this pathway helps V. cholerae prioritize survival over growth, making it a key target for intervention.”

Beyond Cholera

Cholera remains a major problem in regions lacking clean drinking water, and Vibrio cholerae serves as a key model for studying infectious diseases. However, Nguyen noted that studying infections can be challenging, as biofilm lifecycles vary across species. To see if the pathway controlling biofilm formation in V. cholerae exists in other bacteria, Bridges and Nguyen collaborated with M. R. Pratyush, a graduate student in N. Luisa Hiller’s lab, who conducted a bioinformatic analysis. They discovered that the biofilm-regulating protein—and its multi-protein module—is conserved across many bacterial species, suggesting a shared mechanism that could be targeted to influence bacterial behavior.

Building on this, the team partnered with researchers at the University of Pittsburgh to examine how protein interactions in this pathway affect bacterial lifestyle decisions, and with Tufts University School of Medicine to test its role in infection. In mice, bacteria with an activated pathway (mutant strains) struggled to grow and colonize hosts [1]. “Our goal is to activate this pathway to weaken bacteria, and we are searching for small molecules that can turn it on,” Nguyen explained.

Looking ahead, Bridges emphasized translating basic science into therapeutics: “We’ve always focused on understanding bacterial biology, but antibiotic resistance is a crisis. Developing new treatments that work differently is the direction we’re headed.”

References:

1. https://phys.org/news/2025-12-bacterial-decision-outsmart-antibiotic-resistance.html

Cite this article:

Janani R (2025), Targeting Bacterial “Decision-Making” to Combat Antibiotic Resistance, AnaTechMaz, pp. 642