New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
dlf
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New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by dlf » Fri 18 Sep 2015 0:13

New study from Ying Zhang and colleagues:

Free full-text:
http://www.mdpi.com/2079-6382/4/3/397/htm

PDF download:
http://www.mdpi.com/2079-6382/4/3/397/pdf

Antibiotics 2015, 4(3), 397-410; doi:10.3390/antibiotics4030397

Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, David Sullivan and Ying Zhang *
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA;
Abstract: Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive oxygen species production are more active against the B. burgdorferi persisters than the commonly used antibiotics that inhibit macromolecule biosynthesis. Future studies are needed to evaluate and optimize the promising active hits in drug combination studies in vitro and also in vivo in animal models. These studies may have implications for developing more effective treatments of Lyme disease.

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ChronicLyme19
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by ChronicLyme19 » Wed 23 Sep 2015 3:24

Interesting excerpts:
However, according to the CDC, about 10%–20% of patients receiving this treatment experience chronic symptoms such as fatigue, muscle pain, and neurological impairment even six months after treatment [5], but a more recent study estimated the percentage of such patients to be at least 20% [6].
The cause of PTLDS is unknown. Several theories have been proposed to explain this syndrome, including host response to continued presence of bacterial debris, autoimmunity, co-infections, and bacterial persisters not killed by the current Lyme antibiotics [8].

Evidence that supports the continued presence of persisting organisms despite antibiotic treatment has been well documented in various animal models such as mice, dogs, and nonhuman primates [9,10,11,12]. Intriguingly, the organism could not be cultured in conventional culture medium after antibiotic treatment but could be detected by more sensitive and indirect techniques such as xenodiagnosis and PCR. Similarly, in patients with chronic Lyme infections, signs of persisting organisms in a nonculturable form could be detected by positive PCR and xenodiagnosis [13]. Persistent bacteria are suggested as an explanation for the chronic symptoms of PTLDS as well as the observations of B. burgdorferi DNA without positive culturing results [14,15].
Their claims are getting bold now!
We plan to validate these results using clinically relevant dosages in future drug combination studies in vitro and in vivo.
:woohoo:
Half of what you are taught is incorrect, but which half? What if there's another half missing?

Lorima
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by Lorima » Thu 14 Jan 2016 0:38

I missed this in September. No Auwaerter as co-author this time.

This may be the first time that someone at a top-tier academic medical institution in the US has succeeded in publishing a paper about LD that I consider to be straightforward, reasonable and potentially helpful. (Though Dr. Aucott, also at Hopkins, may have paved the way.) I guess the question is not so much why did it take so long, but how did they manage it? And will they survive? ;)
"I have to understand the world, you see."
Richard Feynman

hv808ct
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by hv808ct » Thu 14 Jan 2016 16:33

Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library
Postby Lorima » Thu 14 Jan 2016 0:38

I missed this in September. No Auwaerter as co-author this time.
This may be the first time that someone at a top-tier academic medical institution in the US has succeeded in publishing a paper about LD that I consider to be straightforward, reasonable and potentially helpful. (Though Dr. Aucott, also at Hopkins, may have paved the way.) I guess the question is not so much why did it take so long, but how did they manage it? And will they survive?
Lyme patient/activists aren’t known for subtlety or understatement, but this may be the biggest bit of hyperbole ever posted about LD.

You must have pretty high standards for published work if you’re dismissing 35 years worth of public research and the 10,558 papers, reviews and letters listed in PubMed. How is this paper “straightforward, reasonable and potentially helpful” when it deals with the very old subject of lag-phase bacteria and their greatly diminished metabolism? As with similar studies using mycobacteria, staph, and pseudomonas, it’s a reminder that absent a functional immune system all the antibiotics in the world are not going to eliminate an infection.

“How did they manage it?” The same way they managed earlier studies using bacteria other than Bb.

“Will they survive?” Survive what? I don’t think a handful of tenured and published PhDs, MDs, and a technician are in much danger of anything—real or imagined—except maybe the morning rush hour traffic around Hopkins Medical.

Lorima
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by Lorima » Fri 15 Jan 2016 16:00

Will they survive the potential professional suicide of contradicting a heavily defended article of medical dogma, in this case the belief that there are no Bb persisters that a normal immune system can't destroy, after an IDSA-recommended course of antibiotics?

It's funny how much rhetorical (and even scientific) license you grant yourself and your team. And then you pretend not to understand what I mean by "survive" here. Is this a conscious part of your disinformation campaign, or can you really not see the hypocracy there? I'm still on the edge, in the "fool" vs "bully" judgment (though one does not exclude the other; in fact I guess I think all bullies are fools, though they often succeed in being very destructive.) It's true that completely unconscious bias is a huge factor in medical errors and fraud, and I generally assume that everyone, however wrong and even cruel, has a rationale by which they think they are acting to preserve some "greater good". But your constant sarcasm makes me think you just enjoy being aggressive toward the less powerful in general, and the LD controversy is a merely a good opportunity for you to indulge that vice.
"I have to understand the world, you see."
Richard Feynman

Henry
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by Henry » Fri 15 Jan 2016 17:38

Lorima; Your comments provide a splendid example of "the pot calling the kettle black".

Lorima
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by Lorima » Fri 15 Jan 2016 18:12

And now we can argue about who started it. ;)
"I have to understand the world, you see."
Richard Feynman

hv808ct
Posts: 256
Joined: Wed 30 Jul 2008 4:11

Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by hv808ct » Fri 15 Jan 2016 23:15

Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library
Post by Lorima » Fri 15 Jan 2016 16:00

Will they survive the potential professional suicide of contradicting a heavily defended article of medical dogma, in this case the belief that there are no Bb persisters that a normal immune system can't destroy, after an IDSA-recommended course of antibiotics?

It's funny how much rhetorical (and even scientific) license you grant yourself and your team. And then you pretend not to understand what I mean by "survive" here. Is this a conscious part of your disinformation campaign, or can you really not see the hypocracy there? I'm still on the edge, in the "fool" vs "bully" judgment (though one does not exclude the other; in fact I guess I think all bullies are fools, though they often succeed in being very destructive.) It's true that completely unconscious bias is a huge factor in medical errors and fraud, and I generally assume that everyone, however wrong and even cruel, has a rationale by which they think they are acting to preserve some "greater good". But your constant sarcasm makes me think you just enjoy being aggressive toward the less powerful in general, and the LD controversy is a merely a good opportunity for you to indulge that vice.
Response 101: attack the messenger, ignore the message.

How does one commit professional suicide by noting the existence of lag-phase bacteria and the importance of functional innate and adaptive immune responses? And how could a professional society devoted to one medical specialty (i.e., the IDSA) play a role in “professional suicide” at a major medical institution? Are there any examples of the IDSA assisting in any such a suicide or is this just another example of fantastic fantasy and hyperbole from a conspiracy-minded group of people. Pretty wacky thinking if you ask me. It would be as if AAAS or ASM tried to get me fired because I disagreed with one of their policies on federal funding or special pathogens or experiments on gain-of-function. It’s silly. But then this is a country well known for paranoid thinking and anti-intellectualism.

duncan
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by duncan » Fri 15 Jan 2016 23:23

hv808ct, regarding your last sentence, I refer you to Henry's last sentence.

Lorima
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Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

Post by Lorima » Sat 16 Jan 2016 2:17

:)
"I have to understand the world, you see."
Richard Feynman

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