A new approach could herald a shift in the way we use antibiotics. By attacking the pathogen's unique and hidden metabolic 'vulnerabilities,' researchers offers a new tool in the global challenge to counteract antibiotic resistance and uncover similar combination therapies for other diseases.
A new approach could herald a shift in the way we use antibiotics. By attacking the pathogen's unique and hidden metabolic 'vulnerabilities,' researchers offers a new tool in the global challenge to counteract antibiotic resistance and uncover similar combination therapies for other diseases.
Princeton Chemistry's Seyedsayamdost Lab offers a promising treatment for this neglected tropical disease with a combination of low-dose antibiotics that targets the pathogen but leaves gut microbiome bacteria unscathed. "Low-dose or subinhibitory doses of antibiotics don't affect growth of the pathogen but have a significant impact on its physiology and metabolism. And once we noticed that, we took advantage of this very unique response to combat an organism that is really difficult to kill."Proceedings of the National Academy of Sciences
"This work also reinforces how important it is to think beyond traditional boundaries in science," added Zhang, now a medical student at Robert Wood Johnson."Combining ideas from the oncology space with our knowledge of microbiology and microbial metabolism, required us to challenge a lot of assumptions about how antibiotics 'should' work. It's exciting to see those risks pay off with a discovery that could genuinely help patients.
"Basically we accomplished the molecular version of synthetic lethality, a well-known genetics phenomenon, wherein two mutations are only deadly when combined," said Seyedsayamdost."You add one molecule, it has no effect. You add a second molecule, it has no effect. But you combine the two molecules -- in this case, trimethoprim and DHL -- and the combination is deadly. We mixed genetics and chemistry, and it worked.
Wounds And Healing Pharmaceuticals Bacteria Microbes And More Microbiology Chemistry Organic Chemistry Biochemistry
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