Cornell Biologists Discover Novel Bacterial Weakness, Paving Way for New Antibiotics
Cornell University researchers have identified a fundamental vulnerability in bacteria, potentially opening a new avenue for antibiotic advancement that could circumvent growing drug resistance. The study, recently published in mBio (July 2025), details how manipulating bacterial metabolism can disrupt cell wall formation, effectively crippling and killing the microbes.
Led by postdoctoral fellow Megan Keller in the laboratory of Associate Professor Tobias Dӧrr, the team focused on Vibrio cholerae, the bacterium responsible for cholera. While known for its resilience to certain antibiotics,V. cholerae exhibited meaningful growth defects when engineered to accumulate specific sugar-phosphates.
Chemical analysis revealed these sugar-phosphates directly interfered with the enzymes responsible for building peptidoglycan – the essential,rigid meshwork forming the bacterial cell wall. As sugar-phosphate levels increased, the cell wall’s construction was severely compromised, rendering the bacteria fragile and prone to bursting.
Notably, this disruption mirrors the affect of existing antibiotics that target cell wall synthesis, but operates through a completely distinct mechanism.This difference is crucial, as it may reduce the likelihood of bacteria developing resistance. Instead of directly attacking bacterial enzymes, the research suggests a strategy of inducing toxic sugar-phosphate accumulation.
“We shut down the bacterium’s ability to eat sugar,while simultaneously occurring,sensitize it to cell-wall targeting antibiotics,” explained Keller. ”This will make it harder for them to develop resistance.”
The research, which benefited from collaborations with Weill Cornell Medicine experts in metabolomics, genetics, and biochemistry, highlights the potential for therapies that exploit this metabolic weakness. Becuase peptidoglycan is vital for bacterial survival but absent in human cells, such therapies could selectively target bacteria without harming the host. Though, researchers acknowledge the potential for impacting beneficial microbes as well.
Dӧrr emphasized the broader implications of the findings: “This work shows us that bacteria carry the seeds of thier own destruction. Exploring synergies between antibiotics and metabolic perturbations is an emerging field, holding great promise for the development of novel therapies.”
The Cornell team is now focused on determining if this mechanism is conserved in othre pathogenic bacteria and screening for compounds that can effectively boost sugar-phosphate levels.The ultimate aim is to translate these fundamental discoveries into new antibiotic strategies capable of overcoming the escalating challenge of antibiotic resistance.
