Researchers at Merck have found a way to return antibacterial efficacy to agents that have lost their ability to kill certain types of bacteria. In a paper published in Science Translational Medicine, the team describes a search for molecules capable of interfering with one of the main defense mechanisms that bacteria have developed to resist antibacterial drugs.
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of staph infections and has become immune to attack by beta-lactam antibiotics, which include penicillin. Research has shown that one of the ways MRSA wards off beta-lactams is by fortifying its cell walls with “building blocks” made of teichoic acid. Scientists have long known about molecules that can disrupt the building of such walls in their latter stages, but so far these molecules have not proven to be effective in helping reduce drug resistance in MRSA.
In the new study, researchers searched for molecules capable of interfering with the early stages of cell-wall development by building each molecule from scratch and testing it with another chemical that was known to inhibit later-stage growth. The team reported that two molecules they created––tarocin A and B––could interrupt wall building at an early stage, which allowed a dose of beta-lactams to move in for the kill.
Once the two molecules had been identified, the team worked to bolster their wall-busting effects. They then conducted multiple tests of the abilities of both molecules to help treat bacterial infections.
The investigators found that the molecule/beta-lactam combinations were successful in 82% of laboratory samples tested against MRSA. The combinations were also 72% effective against another common drug-resistant bacterium, methicillin-resistant S. epidermidis (MRSE). The researchers then tested the combinations in mice infected with MRSA. Animals that received the double-dose treatment showed signs of reduced infection, whereas those given just one of the drugs did not improve at all. Further, the researchers reported that neither of the new molecules appeared to harm human cells.
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