Modified Antibiotic Drug Helps In Fighting The Drug Resistance
- Author: Joanne Flowers Jun 03, 2017,
Jun 03, 2017, 9:05
Since the discovery of penicillin began the antibiotic revolution in 1928, we have lived in a golden age of relative safety from infection. VRE is listed as being high priority on the World Health Organization's ranking of bacteria which most urgently need research and development into new antibiotics.
"Vancomycin was disclosed in 1956 and introduced into the clinic in 1958", the researchers said. Putting the three modifications together produced a drug that is 6,000 times as potent against vancomycin-resistant enterococci (VRE) as the original.
Thousands of people die each year in the USA from antibiotic resistant infections, according to the Centers for Disease Control and Prevention, and if the problem worsens, millions could die from minor, easily transmitted infections, according to projections. All three modifications alone make the drug more potent and enable it to kill vancomycin-resistant bacteria, and the potency increases with each modification, but the drug packs its biggest punch when the modifications are combined. "With these modifications, you need less of the drug to have the same effect", Boger said in a statement. The old molecular drug is modified to improve it to better for attacking bacteria where it hurts thus destroying cell walls.
"Organisms just can't simultaneously work to find a way around three independent mechanisms of action", he says.
"This compound exhibited the most potent inhibition of cell wall synthesis in the assay of all compounds assessed as well as the most pronounced and potent induced cell membrane permeability of all compounds examined".
They also found that they could create another modification, which would involve a different way of disrupting bacterial cell walls. Image credit: Okano et al, doi: 10.1073/pnas.1704125114.
'Even if they found a solution to one of those, the organisms would still be killed by the other two'.
One of the infections that is hard to treat and that has put doctor into trouble is vancomycin-resistant enterococci or VRE.
While fear of losing antibiotics has made doctors restrict their use, Boger and colleagues contend that doesn't solve the problem, it just slows the process. The next step is to come up with a way to synthesize the modified vancomycin using fewer steps in the lab, because the current method takes 30 steps. "It's nearly like having a new antibiotic". The researchers say they now have no indication that this newer vanco would be overly toxic to mammals, but that will still need to be tested. In fact, the World Health Organization considers it to be one of the most risky drug-resistant bacteria on Earth. And resistance to such an antibiotic would be very hard to emerge.
While the effectiveness of vancomycin is boosted by these modifications, so is its ability to fend off the evolutionary forces of resistance.
"This is going to be one small step on a long road to trying to tackle antibiotic resistance", Garner said.