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

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

About 700,000 people worldwide die each year from antibiotic-resistant bacteria. According to the World Health Organization, the world can see about 10 million deaths per year from resistant bacteria by 2050, without new types of treatment. Many different types of bacteria, from gonorrhea to salmonella, are becoming more resistant to our drugs. It is a problem that all countries will have to deal with.

The seemingly obvious solution for bacteria becoming resistant to our antibiotics would be to develop new antibiotics, but this is not as simple as it may seem. Not only is it difficult and expensive to develop new antibiotics, but pharmaceutical companies see no incentive to invest in it.

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

“Its lifespan is so short because of resistance to multiple drugs, and WHO says we should save new antibiotics for the last resort, so why would you want to invest a billion dollars and 10 to 15 years in developing something that will be used as a last resort? ”Strathdee said. “They are not going to make money from it.”

If we want pharmaceutical companies to develop new antibiotics, we need to change the incentive structure. Strathdee said that a bill that is in Congress, called the PASTEUR Act, would do just that. It would cause pharmaceutical companies to be paid based on the social value of the antibiotics they create, rather than being paid based on the amount of pills they sell. Congress would allocate $ 11 ($ 15) billion to this program over a 10-year period. Strathdee said he expects this to go through the Biden government.

“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.”

In addition to creating new antibiotics, Strathdee says we need to support research on phage therapy. A phage is a virus that naturally infects and kills a specific type of bacteria. If you create the right “phage cocktail” as it is called, you can inject billions of these phages into someone’s bloodstream and, ideally, cure your infection without killing other types of bacteria that may be beneficial. These phages basically do one thing, so they are not harmful to humans when used correctly. Strathdee entered 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 her life.

“First of all, we need clinical trials to ensure that phage therapy is proven to be effective so that the FDA can license it so that it no longer has the experimental label, because now it is a case-by-case basis that they have to approve it” said Strathdee.

Strathdee and his colleagues at the Center for Innovative Phage Applications and Therapeutics are preparing to conduct the first clinical trial of phage therapy funded by the National Institutes of Health. Not only can you use natural phages to fight bacteria that are resistant to antibiotics, but Strathdee said we should also focus on using genetically modified phages and synthetic phages.

“Metagenomics allow you to put different pieces of DNA together and create a synthetic phage,” said Strathdee. “I think a combination of natural phage, genetically modified phage and synthetic phage will be needed in the future to be able to deal with the entire repertoire of pathogens that are affecting human health.”

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, assistant professor of biomedical engineering at Penn State and one of the authors of a new study on this technique, told Gizmodo that you can create peptides to kill a type of bacteria and leave useful bacteria alone.

“These peptides that we are manufacturing belong to a class called antimicrobial peptides. Any peptide that kills bacteria effectively is called an antimicrobial peptide, ”said Medina. “The only result of what we did was that we designed one that selectively kills that specific pathogen. In that case, it was tuberculosis. We designed the peptide to selectively kill this microbe and prevent the nonspecific death of other bacteria around it. “

Medina believes that the use of peptides to kill bacteria may be superior to the use of phages, because phages typically target specific receptors or ligands to find and kill bacteria, and bacteria can evolve to alter these characteristics to avoid phages. With peptides, it is attacking the real “cell envelope,” Medina said, which should make it harder for bacteria to avoid.

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

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

“In 10 to 20 years, unless we have a game-changing technology, I think we will see that drug-resistant bacteria are causing more deaths than cancer,” said Medina. “I don’t think there is any magic solution for resolving antimicrobial resistance. I think that if we develop therapies that are more difficult for bacteria to develop resistance, it means that we can use those therapies longer. “

Unfortunately, the covid-19 crisis meant that many resources and attention that would be devoted to this problem were dedicated to fighting the pandemic. Strathdee said we have also seen antibiotic overuse far more than usual because doctors are trying to prevent covid-19 patients from contracting a secondary infection.

“There is a concern that people with greed who have been in hospitals, especially if they have been on the ventilator, are prone to secondary bacterial infections, so doctors are using excess antibiotics to try to prevent these bacterial infections from occurring, and are using them even when they are not needed, ”said Strathdee.

The covid-19 pandemic is obviously a major threat that we need to face. However, this is not only diverting resources from tackling the problem of antibiotic-resistant bacteria, but it is also contributing to that problem. When the pandemic is over, we will need to step up our efforts to address this other threat. Strathdee and Medina say they hope to learn from this pandemic that we need to prepare for the next public health crisis and do everything we can to prevent it, so that we don’t end up in the type of disaster that we are in now.

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