From Knowable Magazine, September 9:
In promising experiments, phage therapy forces bacteria into a no-win dilemma that lowers their defenses against drugs they’d evolved to withstand
Peering through his microscope in 1910, Franco-Canadian microbiologist Félix d'Hérelle noticed some “clear spots” in his bacterial cultures, an anomaly that turned out to be viruses preying on the bacteria. Years later, d'Hérelle would come to use these viruses, which he called bacteriophages, to treat patients plagued with dysentery after World War I.
In the decades that followed, d'Hérelle and others used this phage therapy to treat bubonic plague and other bacterial infections until the technique fell into disuse after the widespread adoption of antibiotics in the 1940s.
But now, with bacteria evolving resistance to more and more antibiotics, phage therapy is drawing a second look from researchers — sometimes with a novel twist. Instead of simply using the phages to kill bacteria directly, the new strategy aims to catch the bacteria in an evolutionary dilemma — one in which they cannot evade phages and antibiotics simultaneously.
This plan, which uses something called “phage steering,” has shown promising results in initial tests, but the scope of its usefulness remains to be proven.
There’s certainly need to find new ways to respond to bacterial infections. More than 70 percent of hospital-acquired bacterial infections in the United States are resistant to at least one type of antibiotic. And some pathogens, such as Acinetobacter, Pseudomonas, Escherichia coli and Klebsiella — classified by the World Health Organization as some of the biggest threats to human health — are resistant to multiple antibiotics. In 2019, antibacterial resistance was linked to 4.95 million deaths globally, heightening the call for more effective treatment options.
One of the ways that bacteria can evolve resistance to antibiotics is by using structures in their membranes that are designed to move unwanted molecules out of the cell. By modifying these “efflux pumps” to recognize the antibiotic, bacteria can eliminate the drug before it poisons them.
As it turns out, some phages appear to use these same efflux pumps to invade the bacterial cell. The phage presumably attaches its tail to the outer portion of the pump protein, like a key slipping into a lock, and then injects its genetic material into the cell. This lucky coincidence led Paul Turner, an evolutionary biologist at Yale University, to suggest that treating a patient with phages and antibiotics simultaneously could trap bacteria in a no-win situation: If they evolve to modify their efflux pumps so the phage can’t bind, the pumps will no longer expel antibiotics, and the bacteria will lose their resistance. But if they retain their antibiotic resistance, the phages will kill them, as Turner and colleagues explained in the 2023 Annual Review of Virology....
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