Pathogens play a deadly game of chess, especially when the troublesome bacteria becomes drug resistant. The bacteria can alter the shape of the active site on its enzyme and render its host defenseless. This change can prevent drugs from binding to it.
Duke University researchers are using computer programs to predict just how bacteria develop resistance, hoping this knowledge would help create more robust drugs that could win despite any last minute changes in the bacteria.
That way, bacteria like methicillin-resistant Staphylococcus aureus (MRSA) -- which is prevalent in hospitals -- would have a harder time gaining resistance to the drugs that were designed to treat the infection in the first place.
“We are excited about the prediction power we have, in this case with MRSA, because we used a sophisticated algorithm that models protein and drug flexibility while searching for mutants,” Bruce Donald at Duke University said in a statement.
In this particular study, the researchers looked at the MRSA enzyme called dihydrofolate reductase (DHFR) -- which is the site that drugs bind to. The program predicts how the enzyme could change by considering all of the possible scenarios and chemical reactions that could occur.
“The protein-design algorithms that predict mutations could be used in a drug-design strategy against any pathogen target that could gain resistance through mutation. It’s very expensive and labor-intensive to go back to square one and redesign a drug when a bacterium gains resistance to a drug’s existing structure,” Donald said. The researchers are releasing their program and will make it open source.
“My kids are now nine and 11, and when I ask about the antibiotics they took 10 years ago, I’m now told these are not strong enough to treat the same illnesses, which is a real-life example of drug resistance,” Donald added.
We risk returning to an era before antibiotics. Now, that's the real danger.
As bacteria becomes drug resistant, doctors are thinking about treating patients with once-considered-risky, old-school antibiotics.
"People are going all the way back to the original antibiotics that were shelved because of toxicity. We are desperate," said John S. Bradley, a pediatric infectious disease specialist at the UC San Diego School of Medicine.
The impulse to reexamine the older antibiotics is all the stronger because relatively few new antibiotics are in the development pipeline. And, because the old ones have not been heavily used in recent years, bacteria have not had much chance to develop resistance to them.
While a patient might end up in a hospital room, the root of the antibiotic resistance might begin on a farm. Time magazine reports: