The BBC News article Ultra-tough antibiotic to fight superbugs says (in part):
One hard-to-treat infection that has been worrying doctors is vancomycin-resistant enterococci or VRE.
It has been found in hospitals, can cause dangerous wound and bloodstream infections and is considered by the WHO to be one of the drug-resistant bacteria that pose the greatest threat to human health.
Some antibiotics still work against VRE, but the 60-year-old drug vancomycin is now powerless.
The Scripps team set out to see if they could revamp vancomycin to restore its killing ability.
They made some strategic modifications to the molecular structure of the old drug to make it better at attacking bacteria where it hurts - destroying cell walls.
Three changes in particular seem to be important, increasing the strength and durability of the drug.
Lead researcher Dr Dale Boger explained: "We made one change to the molecule vancomycin that overcomes what is the present resistance to vancomycin. And then we added to the molecule, two small changes that built into the molecule, two additional ways in which it can kill bacteria. So the antibiotic has three different, we call them 'mechanisms', by which it kills bacteria. And resistance to such an antibiotic would be very difficult to emerge. So it's a molecule designed specifically to address the emergence of resistance." (emphasis added)
Unfortunately I haven't been able to see the PNAS paper. The link in the BBC article just gives me this:
However the title in PNAS seems to be stated in the Genetic Engineering & Biotechnology News article Vancomycin Modified to Combat Growing Antibiotic Resistance Threat as "Peripheral Modifications of [Ψ[CH2NH]Tpg4]Vancomycin with Added Synergistic Mechanisms of Action Provide Durable and Potent Antibiotics"
It sounds to me that the first change was to keep the original vancomycin's original mode of action but to make it more robust against adaptations in the vancomycin-resistant strain, but I'm not sure if that's correct.
The other two differences sound to me like two new mechanisms that were not there before - it almost sounds like they could just as well be on different molecules administered simultaneously, and that their presence on the vancomycin molecule is primarily for issues of delivery.
Are these two new changes essentially independent modes of actions that could be on separate molecules, or do they need to reside on the same molecule as the primary mechanism?
The article puts the word "mechanism" in quotes. I'm trying to understand if these are independent or work together at the molecular level - in other words do they operate together in such a way that they need to be on the same molecule?