Study uncovers new findings on antimicrobial drug synergy

March 27, 2018, University of Minnesota
A black and white X-ray picture showing a triangular white area on the left side. A circle highlights the area. Credit: James Heilman, MD./Wikipedia

New data from a study led by researchers from the University of Minnesota Medical School could change how future antimicrobial drug combinations are discovered and developed.

Trimethoprim-sulfamethoxazole is a highly synergistic antimicrobial drug combination that is widely used to treat a variety of bacterial and fungal infections. These drugs are known to act by targeting specific steps in the folate biosynthetic pathway, and their combined activity is far greater than the sum of their individual activities. For the last fifty years it has been presumed that the basis for their synergistic antimicrobial activity was fairly simple—essentially, that the drugs work together by inhibiting sequential steps in a linear biosynthetic pathway.

A new study from Yusuke Minato, PhD, and Anthony D. Baughn, PhD, from the Department of Microbiology and Immunology at the University of Minnesota Medical School, demonstrates that there is an unrecognized cyclic pathway structure within the folate biosynthesis pathway, the target of these drugs, that allows each drug to enhance the activity of the other.

"We now understand how these two antibiotics work together. An overlooked loop structure of the folate biosynthetic is crucial to produce synergistic activity of these two antibiotics," said Minato.

This discovery, recently published as a paper, "Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole" in Nature Communications, has the potential to open new doors for identification of other synergistic .

"It tells us the way we can look for other drug combinations that will have similar synergistic ," said Baughn. "There is a major problem with drug resistance and lack of effective drugs, not just for Escherichia coli where our work was focused, but for pretty much all infectious diseases."

Drs. Baughn and Minato hope that the understanding of mechanisms for synergy will lead them and others to more potent drug combinations that can be deployed in the fight against pathogenic microbes as resistance becomes increasingly commonplace.

Explore further: Novel algorithm predicts drug combinations to treat drug resistant fungal infections

More information: Yusuke Minato et al, Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole, Nature Communications (2018). DOI: 10.1038/s41467-018-03447-x

Related Stories

When HIV drugs don't cooperate

October 2, 2017

The term "synergy" has gained a reputation as an overused buzzword, but it has a quantifiable definition in pharmacology. Two drugs are considered synergistic when their effectiveness when used together is greater than the ...

New method to measure how drugs interact

October 17, 2017

Cancer, HIV and tuberculosis are among the many serious diseases that are frequently treated with combinations of three or more drugs, over months or even years. Developing the most effective therapies for such diseases requires ...

Recommended for you

Archaeologists discover Incan tomb in Peru

February 16, 2019

Peruvian archaeologists discovered an Incan tomb in the north of the country where an elite member of the pre-Columbian empire was buried, one of the investigators announced Friday.

Where is the universe hiding its missing mass?

February 15, 2019

Astronomers have spent decades looking for something that sounds like it would be hard to miss: about a third of the "normal" matter in the Universe. New results from NASA's Chandra X-ray Observatory may have helped them ...

What rising seas mean for local economies

February 15, 2019

Impacts from climate change are not always easy to see. But for many local businesses in coastal communities across the United States, the evidence is right outside their doors—or in their parking lots.

The friendly extortioner takes it all

February 15, 2019

Cooperating with other people makes many things easier. However, competition is also a characteristic aspect of our society. In their struggle for contracts and positions, people have to be more successful than their competitors ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.