A team of researchers at the University of California, San Francisco (UCSF) has engineered new versions of a bacterial enzyme that could lead to the development of more potent antibiotics. The enzyme, called dihydrofolate reductase (DHFR), is essential for the growth and survival of many bacteria. By modifying DHFR, the researchers were able to make it more susceptible to inhibition by antibiotics, which could make it easier to kill bacteria.

The findings, published in the journal Nature Chemical Biology, could have important implications for the treatment of bacterial infections, which are a major cause of death and illness worldwide. Antibiotics are commonly used to treat bacterial infections, but they are becoming less effective as bacteria develop resistance to them. The new findings could lead to the development of new antibiotics that are more effective at killing bacteria and less likely to cause resistance.

DHFR is an enzyme that helps bacteria convert dihydrofolate to tetrahydrofolate, which is a cofactor for several important metabolic reactions. By modifying DHFR, the researchers were able to make it more susceptible to inhibition by methotrexate, an antibiotic that is commonly used to treat cancer. The modified DHFR was also more susceptible to inhibition by other antibiotics, such as trimethoprim and sulfamethoxazole.

The researchers believe that the new findings could lead to the development of new antibiotics that are more effective at killing bacteria and less likely to cause resistance. They are currently working on developing new antibiotics based on the modified DHFR.

"We are excited about the potential of these findings to lead to the development of new antibiotics," said study lead author Dr. Peter Dervan. "Antibiotic resistance is a major threat to public health, and we need new ways to fight bacteria."

The study was funded by the National Institutes of Health (NIH).