New antibiotic shows long-lasting promise as superbug killer
Antibiotics have saved countless lives for the better part of a century, but these medical marvels may be approaching the end of their usefulness. Thanks to overuse, bacteria are rapidly evolving resistance to our best drugs, prompting scientists to try to develop new ones. Now, a team at Purdue University has found that a compound called F6 is effective at killing bacteria that have already evolved resistance to existing antibiotics. In tests, the new drug also seems less susceptible to bacterial resistance down the track.
The discovery and use of antibiotics was one of the greatest scientific achievements of the 20th century, as previously-dangerous procedures quickly became safe and infections relatively easy to treat. But after decades of overuse and overprescription, bacteria are fighting back, with more and more antibiotics becoming ineffective – including some of our last lines of defense. If left unaddressed, the problem is predicted to worsen until these so-called superbugs are killing up to 10 million people a year by 2050.
In an effort to stem the tide, researchers are searching for new drug candidates in places as varied as rattlesnake venom, tobacco flowers, honey, maple syrup, berries, fungi, and both human and platypus milk. Other techniques involve developing new bacteria-killing materials, gels, lights and coatings, weakening bugs genetically, or even enlisting predatory bacteria to fight on our side.
The Purdue team has now identified a new candidate, and tested its abilities to develop resistance. The researchers started by scanning through a library of chemical compounds for those with antibacterial properties, settling on one dubbed F6.
The team found that F6 was effective at killing strains of the bacteria Staphylococcus aureus that had developed resistance to antibiotics such as methicillin and vancomycin. But developing new antibiotics is an ongoing arms race, and it's likely that superbugs will eventually evolve resistance to new drugs too.
Thankfully, for now at least, F6 seems to be standing strong against resistance. To test how quickly bacteria could evolve resistance to the new compound, the Purdue researchers exposed methicillin-resistant Staph to F6 in the lab, and measured how the drug's effectiveness changed over time.
"The idea is that if you keep adding increasing concentrations to bacteria and then you keep regrowing the bacteria, after so many cycles you are going to develop resistance," says Herman Sintim, an author on the new study. "Scientists do this to figure out whether whatever they have created develops resistance quickly."
In tests over two weeks, the Purdue scientists monitored the minimal inhibitory concentration (MIC), which is the smallest amount of a drug that is needed to keep a population of bacteria under control. This figure is expected to get higher over time, as it takes more and more of the compound to kill the bugs as they develop resistance.
In this case, the MIC for F6 remained the same for the first nine passages of the test. It then doubled on the 10th day, before staying the same for the rest of the 14-day trial. In the control group of the antibiotic ciprofloxacin, the team found that the drug's MIC tripled after the eighth passage, and by the end of the two-week test more than 2,000 times the amount of the drug was needed.
Suddenly double the dose doesn't sound so bad. Although F6 sounds promising in that regard, there's of course no guarantee that bacteria won't eventually evolve resistance more rapidly. But even so, it's important to stay ahead of the curve.
"We are not saying there will never be resistance to the F6 molecule or analogs thereof," says Simtim. "What we are saying is that here is a new molecule that works and when we try to force resistance we couldn't generate resistance."
In future, the researchers plan to start developing F6 derivatives, in hopes of potentially making the drug even more potent.
The research was published in the European Journal of Medicinal Chemistry.
Source: Purdue University
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