Scientists Are Looking Beyond Antibiotics to Stop the Drug-Resistant Bacteria Crisis

Surgeons in France operate on a patient to inject him with phages as a treatment against multi-drug-resistant bacteria.

Surgeons in France operate on a patient to inject him with phages as a treatment against multi-drug-resistant bacteria.
Photo: ROMAIN LAFABREGUE/AFP (Getty Images)

As the world continues to work toward defeating a pandemic caused by a virus, another type of pathogen is increasingly becoming a major threat. Antibiotic-resistant bacteria has been a growing problem for years due to the overuse of antibiotics in medicine and agriculture, as well as “poor infection prevention and control,” according to the World Health Organization. Researchers say if we don’t develop new ways to kill this kind of bacteria, we could soon lose countless lives every year as our antibiotics fail to treat common infections that can become deadly.

Around 700,000 people across the globe die each year because of antibiotic-resistant bacteria. According to the World Health Organization, the world could see around 10 million deaths per year from resistant bacteria by 2050 without new kinds of treatments. Many different types of bacteria, from gonorrhea to salmonella, are becoming more resistant to our drugs. It’s a problem that every country will have to deal with.

The seemingly obvious solution to bacteria becoming resistant to our antibiotics would be to develop new antibiotics, but that’s not as simple as it may sound. Not only is it difficult and costly to develop new antibiotics, pharmaceutical companies don’t see any incentive to invest in doing it.

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Steffanie Strathdee, associate dean of Global Health Sciences at the University of California, San Diego and author of The Perfect Predator, told Gizmodo that the problem of drug resistance kills the incentive to create new drugs.

“Their shelf life is so short because of multidrug resistance, and the WHO says we should be saving new antibiotics for last resort, so why would you want to invest a billion dollars and 10 to 15 years into developing something that’s going to be used as a last resort?” Strathdee said. “They’re not going to be making any money off of that.”

If we’re going to get pharmaceutical companies to develop new antibiotics, we need to change the incentive structure. Strathdee said a bill that’s before Congress called the PASTEUR Act would do just that. It would have drug companies be paid based on the societal value of the antibiotics they create, rather than them being paid based on how many pills they sell. It would have Congress allocate $11 billion to this program over a 10 year-period. Strathdee said she expects it will pass under the Biden administration.

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Outside of creating new antibiotics, Strathdee says we need to support research into phage therapy. A phage is a virus that naturally infects and kills a specific kind of bacteria. If you create the right “phage cocktail,” as it’s called, you can inject billions of these phages into someone’s bloodstream and ideally cure their infection without killing other types of bacteria that may be beneficial. These phages basically do one thing, so they’re not harmful to humans when used correctly. Strathdee got into phage research when her husband contracted a serious antibiotic-resistant bacterial infection in 2015, and, with the help of phage researchers, she was able to find the right phages to treat her husband’s infection and save his life.

“First, we need clinical trials to ensure that phage therapy is proven efficacious so the FDA can license it so it doesn’t have the experimental label on it anymore, because right now it’s a case-by-case basis that they have to approve it,” Strathdee said.

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Strathdee and her colleagues at the Center for Innovative Phage Applications and Therapeutics are preparing to conduct the first National Institutes of Health-funded clinical trial of phage therapy. Not only can you use natural phages to combat bacteria that is resistant to antibiotics, but Strathdee said we should also be focused on utilizing genetically modified phages and synthetic phages.

“Metagenomics allows you to kind of splice together different bits of DNA and make synthetic phage,” Strathdee said. “I think a combination of natural phage, genetically modified phage, and synthetic phage will be needed in the future to be able to tackle the full repertoire of pathogens that are affecting human health.”

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Similar to phages, a new technique for killing antibiotic-resistant bacteria involves peptides—chains of amino acids—that can target and kill specific types of bacteria. Scott H. Medina, an assistant professor of biomedical engineering at Penn State and one of the authors on a new study into this technique, told Gizmodo that you can engineer peptides to kill one type of bacteria and leave helpful bacteria alone.

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“These peptides we’re making belong to a class called antimicrobial peptides. Any peptide that kills bacteria effectively is called an antimicrobial peptide,” Medina said. “The unique spin on what we did is we engineered one that selectively kills that particular pathogen. In this case, it was tuberculosis. We engineered the peptide to selectively kill that microbe and avoid nonspecific killing of the other bacteria around it.”

Medina believes using peptides to kill bacteria might be superior to using phages, because phages typically target specific receptors or ligands to find and kill bacteria, and the bacteria can evolve to change those characteristics to avoid phages. With peptides, it’s attacking the actual “envelope of the cell,” Medina said, which should make it harder for bacteria to avoid.

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“It’s interacting with the sort of membrane of the cell,” Medina said. “Our belief is that it’s much more difficult for bacteria to evolutionarily adapt to that type of assault, so we think this will translate to these therapies being more difficult for bacteria to develop resistance against.”

Medina and his fellow researchers hope to develop specific peptides to kill many different kinds of bacteria. He said bacteria will likely be able to find ways to avoid being killed by these peptides over time, which is why we need to also develop new antibiotics, invest in phage therapy, and avoid the overuse of antibiotics generally so we’re doing everything we can to face this impending crisis.

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“In 10 to 20 years, unless we have a game-changing technology, I think we’ll see that drug-resistant bacteria are causing more deaths than cancer,” Medina said. “I don’t think there’s any silver bullet that’s going to solve antimicrobial resistance. I think if we develop therapies that are more difficult for the bacteria to develop resistance against, then that means we can use these therapies for longer.”

Unfortunately, the covid-19 crisis has caused a lot of resources and attention that would otherwise be devoted to this problem to be devoted to fighting the pandemic. Strathdee said we’ve also seen antibiotics be overused much more than normal because doctors are trying to prevent covid-19 patients from getting a secondary infection.

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“There’s concern that people with covid who have been in hospitals, especially if they’ve been on the ventilator, are prone to secondary bacterial infections, so physicians are overusing antibiotics to try to prevent those bacterial infections from occurring, and they’re using them even when they’re not necessary,” Strathdee said.

The covid-19 pandemic is, of course, a major threat that we need to address. However, not only is it diverting resources away from fighting the problem of antibiotic-resistant bacteria, it’s actually contributing to that problem. When the pandemic is over, we’ll need to dial up our efforts to face this other threat. Both Strathdee and Medina say they hope we’ll learn from this pandemic that we need to prepare for the next public health crisis and do everything we can to avoid it, so we don’t end up in the kind of disaster we’re in now.

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Thor Benson is an independent journalist who has contributed to Gizmodo, The Daily Beast, The Atlantic, Rolling Stone, Wired and many other publications. Find him on Twitter at @thor_benson.

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