Researchers are groping for a way to get rid of the deadly danger
A superbug epidemic threatens to kill 10 million people a year by 2050. Scientists may have a solution to rid the world of this scourge.
Cynthia Horton's ear pain is the stuff of nightmares, CNN tells CNN. “I can wake up in terrible pain, as if I were having a root canal without anesthesia,” the woman says. “When I sit down, my ear often hurts due to infection, even blood oozes.”
Already weakened by a lifelong battle with lupus, Horton's immune system was destroyed by courses of radiation and chemotherapy following surgery to remove a cancerous tumor in her ear in 2003.
Ear infections became the norm, usually relieved by taking antibiotics. But as the years passed, the bacteria in 61-year-old Horton's ear became resistant to antibiotics, often providing her with little relief.
“These multidrug-resistant superbugs can cause chronic infections in people over months, years, and sometimes decades. It's funny how virulent some of these bacteria become over time,” says Duane Roach, an assistant professor of bacteriophage, infectious diseases and immunology at San Diego State University.
Last year, doctors suggested treating Horton's infection with with the help of one of nature's oldest predators—tiny, tripod-like viruses called phages, designed to seek out, attack, and consume bacteria.
The microscopic creatures have saved the lives of patients dying from superbug infections and are being used in clinical trials as a potential solution to the growing problem of antibiotic resistance. In the United States alone, more than 2.8 million antimicrobial-resistant infections occur each year.
According to 2019 statistics from the US Centers for Disease Control and Prevention, such infections pose “an urgent global public health threat,” killing 5 million people worldwide.
“An estimated 10 million people in year—that's one person every three seconds—will die from a superbug infection,” says infectious disease epidemiologist Steffany Strathdee, co-director of the first dedicated phage therapy center in North America, the Center for Innovative Phage Applications and Therapeutics, or IPATH, at the UCLA School of Medicine. University in San Diego.
Eager to find another solution for her recurring ear infections, Horton was thrilled. Samples of drug-resistant bacteria were sent from her doctor's office in Pennsylvania to IPATH at the University of California, San Diego, in hopes that phage hunters there might find a match. However, what the scientists discovered next was unexpected.
The bacteria cultured from Horton's ear were a perfect match for rare superbugs found in certain brands of over-the-counter eye drops that were robbing people of their sight and their lives.
Suddenly, Horton's search for a solution to his problem took on new meaning. Will the bacteria from her ear help scientists find phages that will also treat eye infections?
Severe cases of antibiotic-resistant eye infections began appearing in May 2022. By January of the following year, the Centers for Disease Control (CDC) reported that at least 50 patients in 11 states had developed superbug infections after using preservative-free artificial tears. By May 2023, the outbreak had spread to 18 states: four people had died, four more had lost their eyes, 14 had suffered vision loss, and dozens more had developed infections in other parts of the body.
“Only a small proportion of patients actually had eye infections, which made the outbreak incredibly difficult to eradicate,” said epidemiologist Dr. Maroya Walters, who led the CDC study on artificial tears. “We have seen people who were colonized with this organism develop urinary tract or respiratory tract infections within a few months, even though they were no longer using these drops. One patient transmitted the infection to others in the health care facility.”
The culprit was a rare strain of drug-resistant Pseudomonas aeruginosa that had never been identified in the United States before the outbreak, the CDC said.
Horton had never used eye drops, but the bacteria isolated from her ear were of the same rare strain. Using these bacteria and other samples sent by the CDC, the IPATH scientists immediately got to work and identified more than a dozen phages that successfully attacked the deadly pathogen.
The CDC scientists were so intrigued by this discovery that they mentioned the availability of phage superbug treatment on the CDC website.
“It got me thinking that when we have an outbreak caused by bacteria with such limited treatment options, should we be thinking about these alternative treatments?” — says Walters.
What is this little creature that can defeat bacteria that can resist all the drugs that modern science can offer? And, more importantly, could phage treatment become a major player in the battle to end the superbug crisis?
Thanks to evolution, billions of bacteria in the modern world have a natural enemy: tiny viruses called bacteriophages, genetically programmed to search and destroy, CNN continues. In this microscopic Terminator game, each set of phages is uniquely designed to seek out, attack and consume a specific type of pathogen.
“Each species of bacteria, or even genotypes, may have a whole set of phages within it that attack it using a wide variety of methods to enter the bacterial cell and weaken it,” says Paul Turner, professor of ecology and evolutionary biology at Yale University and a member of the Yale Department of Microbiology. schools of medicine.
To resist attack, bacteria use various evasive maneuvers, such as shedding their outer shell to eliminate docking ports, which the phage uses to enter, devastate, and ultimately turn the pathogen into pieces of bacterial mucus.
This is good news because newly discovered bacteria may lose resistance to antibiotics, again becoming vulnerable to elimination. However, the phage is disabled and can no longer fight.
To maximize success, experts look for different phages to fight a particularly dangerous superbug — sometimes creating a cocktail of microscopic warriors who can hopefully continue the attack , when one of them is neutralized.
In labs across the United States, phage scientists are taking research and discovery to the next level, or what Strathdee calls “phage 3.0.” Scientists at the Yale Turner Laboratory are busy mapping which phages and antibiotics are most symbiotic in fighting the pathogen. Roach State Laboratory in San Diego is studying the body's immune response to phages while developing new phage purification methods to prepare samples for intravenous administration to patients.
Clinical trials are currently underway to test the effectiveness of phages against intractable urinary tract infections, chronic constipation, joint infections, diabetic foot ulcers, tonsillitis, and persistent, recurrent infections that occur in patients with cystic fibrosis. Chronic infections common in cystic fibrosis are usually caused by various strains of drug-resistant Pseudomonas aeruginosa, the same pathogen responsible for Horton's ear infection and the artificial tear outbreak.
A number of laboratories are developing phage libraries consisting of naturally occurring strains known to be effective against a particular pathogen. In Texas, a new facility is taking evolution one step further by speeding up evolution by creating phages in the laboratory.
“Instead of just getting new phages from the environment, we have a bioreactor that creates billions in real time and billions of phages,” said Anthony Maresso, an assistant professor at Baylor College of Medicine in Houston.
“Most of these phages will not be active against drug-resistant bacteria, but at some point a rare variant will emerge that has been trained to attack resistant bacteria, so to speak, and we will add that to our arsenal,” Maresso said. “This is a next-generation approach to phage libraries.”
Last year, Maresso's lab published a study treating 12 patients with phages tailored to each patient's unique bacterial profile. It was a qualified success: antibiotic-resistant bacteria in five patients were eradicated, while several more patients showed improvement.
To date, genetic manipulation of phages has been difficult due to the optimized nature of the creature: “ Normal phages are optimized by evolution to be lean, mean killing machines. There's very little room for us to step in and change things,” says Elizabeth Villa, a professor of molecular biology at the University of California, San Diego, who is studying a new form of phage called “giant” phages.