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Scientists Found a Way to Make Drug-Resistant Bacteria 'Evolve Backwards'

Use the right antibiotics at the right time can force the bacteria into a pre-resistant state.

by Kaleigh Rogers
May 6 2015, 6:50pm

Image: Nutloak/Flickr

Researchers have proposed a way to force antibiotic resistant bacteria to "evolve backwards" into a pre-resistant state, according to a study published Wednesday in Plos One. It's just one example of the out-of-the-box thinking science is taking to tackle the problem of antibiotic-resistant bacteria before it's too late.

The team of biologists and mathematicians from the University of California Merced, UC Berkeley, and American University teamed up to look at how antibiotic resistant grew along with antibiotics over the last 80 years.

"There was kind of an arms race for about 20 years where pharmaceutical companies just kept changing the cephalosporins (a common antibiotic) and kept changing penicillin to get away from the resistant bacteria," Miriam Barlow, co-author of the study and a biologist at UC Merced, told me over the phone. "But every time they did, the resistance could just evolve."

This left us with a pile of just-slightly-different versions of antibiotics and a pile of bacteria that could be resistant to any of them. Barlow and her colleagues hypothesized that if you treated this bacteria with the right variation of antibiotic, it would force the bacteria to evolve backwards to be resistant to an earlier version. Do this enough times, and the bacteria will only be resistant to the original penicillin or cephalosporin antibiotic. Using mathematical models, they tested this hypothesis and found it was successful.

"If you can identify what bug you've got in the hospital then, in theory, doctors could start biasing the antibiotic usage that's going on in their hospitals towards these antibiotics," Barlow said of the practical implications. "That's kind of already done. What we're doing is giving them a plan for what order they're going to do it in. They haven't really had a guide before now."

Since this hasn't been tested out in a lab setting, Barlow said she's not expecting hospitals to start adopting their process just yet, but it's given the team a good indication that a lab trial would be worthwhile. Fighting bacteria that has evolved to be resistant to antibiotics with old antibiotics might seem counterintuitive, but Barlow's research is a good sign it might just work. And it's just one example of how researchers aren't pulling any punches when it comes to fighting superbugs.

"I [am] going to do all the things that they wouldn't let me do when I was in pharma, which are kind of the crazy ideas"

Like how they partnered biologists with mathematicians for such a hands-on, practical problem. Kristina Crona, a mathematics and statistics professor at American University and co-author of the study, said joining different fields is essential to making progress on this front.

"We have oceans and oceans of information. No brain can look at all that information can process it. You need mathematics for that," Crona told me.

It's similar to an approach a team of researchers at McMaster University in Canada are taking. One of the (many) setbacks is that pharmaceutical companies have stopped investing money in searching for new antibiotics, according to Eric Brown, the Canada Research Chair in Microbial Chemical Biology and one of the researchers at McMaster's infectious disease lab.

"An antibiotic is a victim of its own success in some ways. It's taken for only a week, tops. It's in all likelihood successful so there's no need to take it again," Brown, who previously worked in the pharmaceutical industry, told me. "That just doesn't sound like a good business plan."

So Brown and his colleagues have been searching for different ways of finding new antibiotics. Currently, standard practice is to test out how well a molecule can kill a bacteria in a nutrient-rich environment, where the bacteria can get all the protein and iron and other substances it needs to survive.

But Brown said that's not necessarily the best approach. One of the first antibiotics, Prontosil (a precursor to the so-called sulfa antibiotics we use today) didn't do anything when it was tested in a nutrient-rich environment, but was effective in curing infections when tested on mice. Brown pointed to this as evidence that the status quo might not be showing the whole picture, so he and his colleagues are searching for other ways to test out potential antibiotics.

The team has also investigated different ways of disarming bacteria, like using compounds that bind up the iron in bacteria and kill it from the inside out.

"When I came here I more or less said I was going to do all the things that they wouldn't let me do when I was in pharma, which are kind of the crazy ideas," Brown said. "It's a complex problem and it certainly needs a multi-pronged fix."

All of the researchers I spoke to agreed that there is no single solution that will save us all from the post-antibiotic world the World Health Organization warned us about last year. But by trying to reverse resistance, find new antibiotics, and ending the use of human drugs in the livestock we raise, large groups of the medical community are working in tandem to protect one of the most important medical discoveries in history.

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