why the best way to stop drug-resistant bacteria may be to get them sick

As the world braces for an onslaught of drug-resistant bacteria, we may be closing in on a new weapon against the worst, most persistent strains by domesticating their natural enemies.
bacteriophage

Antibiotic resistance is one of the biggest problems far too few people are taking seriously. As overuse and improper application of antibiotics, especially in the developing world, threaten to give more and more strains of bacteria natural defenses that can beat our best weapons against them, the consequences of doing too little to overhaul how we use and create antibiotics could be devastating. Surgeries and childbirth would be much risker. Infectious diseases that used to kill millions as recently as a century ago would come roaring back. Should our leaders fail to take this threat seriously, as many as 10 million people per year could die prematurely by 2050 from superbugs compared to some 700,000 per year today.

Even worse, Big Pharma has pretty much given up on finding new antibiotics, meaning that we can’t just keep churning out new treatments for nasty bacteria and efforts to get it to realize that we’re dealing with an existential threat are being met with derision and veiled demands for cash advances and tax cuts. So, what can we do? One cutting edge idea is to abandon the idea of antibiotics as we know them and turn to the bacteria’s natural enemy: viruses called phages. By releasing several strains of phages to attack malicious microbes, doctors could, in theory, precisely target the organisms they want to eradicate with biological weapons which evolved to kill them as quickly and efficiently as possible.

Unfortunately, phages are not a perfect tool. Bacterial infections can vary across regions and even individuals, meaning that the phages may not be able to completely eradicate the entire infection unless they’re injected as a specially bioengineered cocktail. Regulatory agencies tend to frown on such complex treatments, and the genetic engineering that would be involved in making the phages more potent could interact with our gut microbes in the process since they are sort of living things, depending on how you see viruses. That said, if the bacteria being targeted evolve resistance to one strain of phages, those phages could evolve new attacks as well, and we’d have almost innumerable strains to choose from.

And now, there’s finally a real-world example of phage therapy in action as a British teen with cystic fibrosis suffering a stubborn infection after a lung transplant was treated with a cocktail of three phage strains. While the researchers aren’t sure whether the bacteria have all been destroyed, the patient made a remarkable recovery and any residual microbes appear to be under control. Armed with some very promising data, they’re now working on adding a fourth strain to their treatment protocol and are looking for new cases in which the phages could save another person fighting abnormally obstinate infections.

It’s a very promising first step decades in the making. The hope is that the phage cocktail could be standardized enough to be widely used, and the available technology could easily let doctors tweak it on a patient by patient basis. This level of personalization and microtargeting could also help slow the spread of bacterial resistance, minimize antibiotic use, and provide a new line of defense for patients for whom standard approaches have failed. Of course, as with any promising new avenue in medicine, there’s a lot of work to do before genetically engineered phages come to a hospital or pharmacy near you, but the important thing is that we’re starting to make some headway against the creeping scourge of antibiotic resistance.

See: Dedrick, R., et. al., (2019) Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus, Nature Medicine, 25, 730–733, DOI: 10.1038/s41591-019-0437-z

# health // antibiotic resistance / medical experiments / medical research


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