New Research into Old Antibiotic May Lead to New TB Treatments

On Dec. 5, 2017, results from a study by the University of Warwick and the Francis Crick Institute were released that show potential for developing new drugs to treat tuberculosis and other related microbial diseases.

The study, led by Professor David Roper at Warwick’s School of Life Sciences and Dr. Luiz Pedro Carvalho from The Francis Crick Institute, focused on understanding how the antibiotic D-cycloserine, an old drug, works for treating microbial diseases on a molecular level. Typically, the drug is considered a secondary treatment option because of adverse side effects associated with its use.

According to the study, D-cycloserine targets multiple bacterial agents in a way unlike any other known antibiotic, by inhibiting two separate enzymes, D-alanine racemase and D-alanine-D-alanine ligase. These enzymes are required to build and maintain the structural integrity of bacterial cell walls. With the D-alanine racemase enzyme, the drug forms a molecular bond with a chemical group required for the enzyme activity, which stops the enzyme from working. Researchers have now observed how D-cycloserine inhibits the D-alanine-D-alanine ligase enzyme for the first time, according to the study.

 “We now understand fully how this antibiotic drug can have totally different methods of working on separate targets. This appears to be unique amongst the antibiotics,” said Roper in a company press release.

“Perhaps more important than how D-cycloserine works, this study highlights an increasingly obvious fact: we know much less than we think about how antibiotics really work and how bacteria become resistant,” said Carvalho in the press release. “Only by truly understanding molecular and cellular events caused by antibiotics or in response to their presence will we truly understand how to make improved drugs, which are much needed in face of the current threat of antibiotic resistance.”

Going forward, researchers aim to use this discovery to target the rise of antibiotic resistance by modifying the structure of D-cycloserine so that it more closely resembles the newly discovered chemical species, which can lead to the creation of an antibiotic that avoids some of the adverse side effects of D-cycloserine.

Source: University of Warwick