Topic: Dormant persister cells - With Lyme disease
steve1906
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. Researchers’ discovery may explain difficulty in treating Lyme disease
June 1, 2015 by Greg St. Martin
Northeastern University researchers have found that the bacterium that causes Lyme disease forms dormant persister cells, which are known to evade antibiotics. This significant finding, they said, could help explain why it’s so difficult to treat the infection in some patients.
“It hasn’t been entirely clear why it’s difficult to treat the pathogen with antibiotics since there has been no resistance reported for the causative agent of the disease,” explained University Distinguished Professor Kim Lewis, who led the Northeastern research team.
In other chronic infections, Lewis’ lab has tracked the resistance to antibiotic therapy to the presence of persister cells—which are drug-tolerant, dormant variants of regular cells.
These persister cells are exactly what they’ve identified here in Borrelia burgdorferi, the bacterium that causes Lyme disease.
The researchers have also reported two approaches—one of them quite promising—to eradicate Lyme disease, as well as potentially other nasty infections.
Lewis and his colleagues presented their findings in a paper published online last week in the journal Antimicrobial Agents and Chemotherapy.
He co-authored the paper with Northeastern doctoral students Bijaya Sharma and Autumn Brown, both PhD’16; recent graduate Nicole Matluck, S’15, who received her Bachelor of Science in Behavioral Neuroscience; and Linden T. Hu, a professor of molecular biology and microbiology at Tufts University.
The research was supported by grants from the Lyme Research Alliance and the National Institutes of Health.
Lyme disease affects 300,000 people annually in the U.S., according to the Centers for Disease Control and Prevention, and is transmitted to people via bites from infected blacklegged ticks. If caught early, patients treated with antibiotics usually recover quickly.
However, about 10 to 20 percent of patients, particularly those diagnosed later, who have received antibiotic treatment may have persistent and recurring symptoms including arthritis, muscle pain, fatigue, and neurological problems. These patients are diagnosed with Post-treatment Lyme Disease Syndrome.
In addition to identifying the presence of these persister cells, Lewis’ team also presented two methods for wiping out the infection—both of which were successful in lab tests.
One involved an anti-cancer agent called Mitomycin C, which completely eradicated all cultures of the bacterium in one fell swoop. However, Lewis stressed that, given Mitomycin C’s toxicity, it isn’t a recommended option for treating Lyme disease, though his team’s findings are useful to helping to better understand the disease.
The second approach, which Lewis noted is much more practical, involved pulse-dosing an antibiotic to eliminate persisters. The researchers introduced the antibiotic a first time, which killed the growing cells but not the dormant persisters.
But once the antibiotic washed away, the persisters woke up, and before they had time to restore their population the researchers hit them with the antibiotic again. Four rounds of antibiotic treatments completely eradicated the persisters in a test tube.
“This is the first time, we think, that pulse-dosing has been published as a method for eradicating the population of a pathogen with antibiotics that don’t kill dormant cells,” Lewis said. “The trick to doing this is to allow the dormant cells to wake up.”
He added: “This gives you an idea that you could, in principle, establish a similar regiment for treating patients for this and other chronic diseases.”
Lewis is a faculty member in the biology department and directs Northeastern’s Antimicrobial Discovery Center. Over the past decade he has led pioneering work on this specialized class of cells produced by all pathogens known as persisters.
Earlier this year, Lewis, biology professor Slava Epstein, and other colleagues published groundbreaking research in Nature presenting a new antibiotic that kills pathogens without encountering any detectable resistance.
In previous work, Lewis’ lab identified a compound called ADEP that causes dormant persister cells in MRSA to self-destruct. This compound was among the first options the researchers tried out to combat Lyme disease.
But it didn’t work, and neither did combinations of standard antibiotics used to treat the disease. The team thought it had hit a dead end yet remained vigilant in its quest to identify promising alternative options.
“What we came up with was the pulse-dosing regimen, which worked beautifully,” Lewis explained. “I think this could be very useful, especially for antibiotics for which resistance doesn’t rapidly develop.”
Though the researchers identified the presence of these persister cells, they also note in their paper that the mechanisms by which the persisters are able to survive remain unknown. More work in this area will be required, they wrote.
-------------------- Everything I say is just my opinion! Posts: 3529 | From Massachusetts Boston Area | Registered: Jul 2008
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Keebler
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- Thanks for posting.
Good to see this. Good work. Still, it's like he's been on another planet to not know that Burrascano (and most ILADS LLMDs) have been incorporating the pulse technique for YEARS
[Pamela Weintraub describes in her book "Cure Unknown" and in her posts how this was of major value to her successful recovery]
This author also must have been on another planet to not consider the cystic / other forms of Bb [or how Bb can get into the bones so the test samples may not show it in any test]
or the work of many ILADS researchers.
Yet, maybe in his isolation, he will see a piece of the puzzle in a different light. But, even with the pulse technique if it ignores how antibiotics can cause development of the cystic form that will require a different classification of drug, as antibiotics won't work (and he's not even looking at that) . . . it may not be as much help.
I'm hoping his eyes will see all that he needs to see . . . and that he will also get to know the work of others in this field but who are not in his inner circle. -
Posts: 48021 | From Tree House | Registered: Jul 2007
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Keebler
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- Pulsed dosing . . . & with combination modalities / various Rx families . . . that worked:
especially see LL author Pamela Weintraub's THREE posts here on Feb. 27 & 28, 2010 (you'll have to scroll down a ways for the third one) -
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steve1906
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. Keebler, I was thinking of you when I posted this, I knew it would get your goat, like it will others too.
That was the fastest reply I ever seen, concidering all the reading and replying.
Good reply.... Steve
-------------------- Everything I say is just my opinion! Posts: 3529 | From Massachusetts Boston Area | Registered: Jul 2008
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Keebler
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- Must have just happened to be online when you posted. And your spacing makes reading easier. Also realized my fridge was off. It' just kicked in and then I cannot think.
Yes, it really gets my goat.
And we are supposed to be, oh, so glad that - finally - someone in the IDSA world is waking up just a little bit that we throw a parade when, really, he's very much behind. Yet, I hope that some piece of this is beneficial.
But, just think how much more good he could do were he to really get up to speed on this. He's years behind and still thinking far too simplistically.
No mention of other forms of Bb or other tick infections that always go along for the ride. How in the world can he be so out of it and still be thought of as on top of his game? -
Posts: 48021 | From Tree House | Registered: Jul 2007
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steve1906
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.
quote:How in the world can he be so out of it and still be thought of as on top of his game?
THE MONEY, for doing nothing!
Steve
-------------------- Everything I say is just my opinion! Posts: 3529 | From Massachusetts Boston Area | Registered: Jul 2008
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Keebler
Honored Contributor (25K+ posts)
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- We need the same folks who investigated the FIFA dishonesty to take a good look at the IDSA.
Oh, legal term required for this point in the process is: 'alleged' dishonest practices -
Posts: 48021 | From Tree House | Registered: Jul 2007
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Is this fancy new term "persisters" another way of describing biofilms?
I will take the quickie 411 if there is a difference. Thanks!
-------------------- unsure445 Posts: 824 | From northeast | Registered: Jun 2008
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Keebler
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- The way I read this . . . (and others may have a different take on it) . . .
is -- unknown to them -
that it's all about a single antibiotic approach that CREATES chronic lyme due killing off some spirochetes but at the same time forcing all those that can scurry to form into cysts (and the illusion that treatment may have worked - even if for a while).
His test tube may have the cystic form develop but he can't see that. And, in a test tube, four rounds may well do the trick but, in a real live person, spirochetes with faced with antibiotics can spring deep into even the bones and then turn into the cystic form.
That's not going to be treated in just four round of a single antibiotic with no attention to the cystic form and with drugs or other agents that can penetrate very deep within.
In addition to the CYSTIC FORM,
BIOFILM does not appear to be what he's talking about - and I doubt they even consider biofilm (as they should, though).
What they are describing in the TEST TUBE likely is the second, third + more waves of spirochetes that are "born" from cyst form after inadequate mono-treatment has lapsed, allowing
the "blooming" of the dormant-only-for-a-while cysts unseen to his eye
that developed in the first place from their oversights:
1. stand alone antibiotic treatment that should have been combination / rotation / pulsed only after the other steps were also incorporated
2. initial treatment for too short a time -
3. without attention to flagyl or the like to also address the cyst form since antibiotics do not kill the cystic form but allow it to thrive
- as well as addressing OTHER forms (more than just the spirochete and cystic form and the kinds of Rx used can be tricky)
4. and also attention to biofilm (which cannot be addressed with antibiotics)
5. Strains also were not considered. Should be.
-- coinfections, of course should be considered but this article is just about borrelia so I'll not go there (and they'd sure never think, too, anyway). -
[ 06-07-2015, 03:13 PM: Message edited by: Keebler ]
Posts: 48021 | From Tree House | Registered: Jul 2007
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Northeastern, huh? He's only about a mile and a half from Allen Steere and all his lackeys. It's a short walk. I'm sure they'll be falling all over themselves to discredit him.
You don't go to Boston if you have Lyme. Steere has a wide range of influence all throughout eastern MA and it's hostile. Been there done that. He's a disgrace to my hometown.
Posts: 99 | From Cali | Registered: Dec 2011
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**and as for Northeastern, all I know about the place is it's a great place to get raging drunk and stupid and to meet girls.
Well, I know a little more about it than that but those were the highlights. The "going to class" part is just a blur.
Posts: 99 | From Cali | Registered: Dec 2011
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From the Northeast to the Midwest and beyond, it’s high season for Lyme disease. An estimated 300,000 Americans are diagnosed with the spreading, tickborne disease every year. Most can be successfully treated with antibiotics, but for some, symptoms persist for months and even years — pain, fatigue, arthritis.
For me, Lyme disease news tends to range from horrifying — stories of insidious, life-ruining symptoms — to just depressing, like recent speculation that New England’s massive snowfall this winter may have insulated ticks and helped them survive.
So, though it’s still extremely early research, I was gladdened by a report just out from Northeastern University that a prominent germ-fighting scientist may have found a new way to kill off Lyme disease bacteria even when it persists after antibiotics. In test tubes, at least.
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