Even for the most elite of bacteria-killers, these superbugs were a challenge.
They’d delayed Mallory Smith from getting a lung transplant, and when she’d finally had the surgery, the bacteria quickly migrated into her new lungs. They shrugged off cocktail after cocktail of antibiotics. Finally, Smith’s father proposed an unusual last resort: finding viruses that parasitize bacteria and injecting them into his daughter. But the experimental treatment came too late. Smith died on Nov. 15, 2017, a little over a month after she’d turned 25.
Yet her bacterial infection lived on, passed from scientist to scientist, from freezer to freezer, traveling from Smith’s hospital room in Pittsburgh, Pa., to a lab in Ann Arbor, Mich., eventually landing in a Petri dish in Jerusalem, some 6,000 miles away. Now, microbiologists at Israel’s Hebrew University have described a new virus that’s especially good at combating Smith’s superbug.
“It’s a phage that kills the strain that killed Mallory,” said Ronen Hazan, who led the team. “This was the best one … and we decided to name it after her.”
It isn’t the first bacteriophage — as such bacteria-fighting viruses are known — that can work against this sort of intractable infection. After all, there are trillions of phages out there, feasting on the bugs that fill our sewage and hunting for hosts in puddles after rain. Even if they’re extreme specialists, attacking only specific strains of a specific species of bacteria, there’s usually more than one that infects a particular superbug. Smith’s doctors had tried out a few that may have done the trick if injected earlier.
Yet the mere fact that researchers are looking for phages to try as therapies is a sign of how much has changed since — and because of — Smith’s death. The hope is that next time there’s a case like hers, a potentially lifesaving treatment will be ready sooner.
The recent surge of phage therapy enthusiasm is a revival of sorts. In the 1930s, you could get phage concoctions to treat everything from dysentery to urinary tract infections to outbreaks of the skin. But then, in the 1940s, penicillin hit the market, and antibiotics became the rage. Eastern European researchers continued to use phages as treatment, but such Soviet science was viewed with suspicion back in the United States.
It was only with the rise of antibiotic-resistant bacteria that Western interest in these viruses-as-treatments began to brew again. Even so, in 2017, many still considered the idea esoteric at best. That was part of the holdup for Smith. There was no established method for finding, purifying, and delivering the viruses her doctors hoped might save her life. When her father reached out to scientists who had a bit of experience with phage therapy, all they could do was send out a frantic flurry of emails and tweets.
Smith’s story helped change that. She’d been born with cystic fibrosis, a genetic illness that fills the lungs with a particularly gluey sort of mucus. Not only does that make it hard to breathe — it also acts as a cushy home for bacteria. When two friends who’d met through swing dancing — one a grad student, the other a tech consultant — read about Smith’s desperate attempt to find a virus that would beat back the bacteria within her, they created an online phage directory to help speed things up. Then, in 2018, the University of California, San Diego, established the first phage therapy center in the U.S.
Yet for a patient with Burkholderia cepacia — the kind of bacterial infection that Smith had — finding the right phage in time is hardly a shoo-in. Partially that’s because it’s not the most common superbug infection, even among cystic fibrosis patients, so not all that many researchers are working on treating it with phage therapy. But it’s also because B. cepacia is an especially tricky type of bacteria to phage-hunt for. Some phages — the ones that are easiest to use as therapies — enter a superbug, replicate like crazy, and cause the host to explode. Others, though, simply integrate peaceably into the bacterial genome. And the phages discovered for B. cepacia often fall in the peaceful-coexistence camp. Plus, for other kinds of bacteria — Pseudomonas, say, or Klebsiella — a phage might be active against a large swathe of strains; for Burkholderia, Hazan explained, the viruses are choosier.
That’s where his lab comes in. The team’s hope is to build up a library of B. cecpacia-killing phages that can be used in cocktails whenever a case like Smith’s pops up. To do that, the scientists have collected all sorts of substances most people would rather not deal with. They take the used saliva, urine, and fecal samples from hospitals. “Instead of discarding them, we take them and search for phages,” Hazan explained. “We’re looking in water bodies, small lakes. After the rain, in puddles. Whenever a student goes on vacation we ask him, ‘Bring some samples of soil or water or whatever!’”
They also regularly take wastewater from West Jerusalem’s sewage treatment plant, which is where the phage active against Smith’s bacteria came from. “Everybody complains about the smell, but we are finding gold in that sewage,” Hazan added.
Three Hebrew University students — Chani Rakov, Ortal Yerushalmy, and Leron Khalifa — first isolated the phage in question this past December. When they put it into a Petri dish covered in the kind of bacteria that had been collected from Smith’s lungs, it began to create clear spots where the superbug was dying off. The decision was unanimous that it should be named BCMallory1, for the initials of the bacteria it’s active against, and the name of the person who helped inspire the search.
When she heard the news, Smith’s mother began to cry. To her, it meant that other families might not have to live through what she did. “It’s a very bittersweet feeling,” said Diane Shader Smith. “You know the suffering, and you don’t want anyone to suffer, but also you think, Mallory could have lived.”
Because bacteria often develop resistance to phages as well, many researchers think it’s best to deliver a cocktail of phages alongside antibiotics, and Hazan plans to keep searching. He’s also thinking about the possibility of genetically engineering some of the phages his team finds, to make them safer or more efficient bacteria-killers.
“We don’t want to have another Mallory Smith,” said Steffanie Strathdee, co-director of the Center for Innovative Phage Applications and Therapeutics, at University of California, San Diego, and co-author of “The Perfect Predator,” a book about how she saved her husband’s life through a similar phage hunt in 2016. Smith’s case still haunts her, she said: “I think about her every day. We came so close to saving her life.”
Is it not co incidentally that i only about five minutes ago wrote my comments and or Memorandum Of Understanding about the Antimicrobial Resistant Super Bugs with the comments earlier and here now on this report Super Bugs are the headline . yes The World Health Organization , [ W .H.O.] wrote the Report about this in the year of 2014 consisting of two hundred fifty seven pages of information  . with the Titled so named Antimicrobial Resistant Super Bugs would be the term ,title or name used to replace the term of name germs to quote unquote , The .W.H.O report . the headline stated that as from the year of 2015 germs would no longer be used ,rather the replacement would be antimicrobial resistant super bugs . for which as of the year 2015 these bugs would kill tens upon tens of thousands of Human Beings to the year of 2020 and costing One Hundred Trillion Dollars to the year 2030 Globally . to quote ,unquote The .[W. H.O ] Report .i did not make this up it is all there for any one to see and read on the . W. H.O web site . question how many times have The Main Stream Media Of The Fourth Estate ,such as The New York Times and others such Alliances of The Press carried this report and others that were published after the year of 2014 . The nation Of China only a few months ago there were reports that over fifty millon pigs had died from the Super Bugs and even more recent .Chickens of more that twelve millions have died from The Swine Flu . yes we are in trouble and only a segment of us human beings are concerned as a significant percent of the Global Population are not rather they are much much more involved or indulge with The Cell , Smart and or Iphones . just look for supporting evidence they have stated that they cannot live with out the three entities listed here and or they do not know what they would do with out them .these states are available in the public domain . i rest my case .Trevor Merchant .Bronx New York City . at 2.26 p.m eastern standard time . Saturday , January . 24. 2020
Great progress finally. Check out new understanding of the importance of biofilm [plaque] in practically all chronic infections. Most bacteria prefer to life in micro-colonies that are 1,000 times more resistant to antibiotics than planktonic organisms. These cells are not dividing and are unculturable. The search is now on for biofilm agents that will open up the biofilm so white cells blood cells can clear the infection.
-Dr. Garth Ehrlich – Twenty Years of Biofilm Research, YouTube 10-05-17: https://www.youtube.com/watch?v=OK-6B2J-si0 length 10:58
-Garth Ehrlich, Focus on Lyme Scientific Conference 2019, YouTube 19-04-16: https://www.youtube.com/watch?v=pKGiEj3OHY8 length 40:50
Biofilm-Leukocyte Cross-Talk: Impact on Immune Polarization and Immunometabolism, Yamada KJ, Kieliant T, J Innate Immun 2019-04;11, 280-288:
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