Onderzoek persister cells

[Sproetje]

Ik ben net pas op de hoogte van het fenomeen percister cells en het verklaart dus ook waarom ik na infusen en orale a.b. een hele tijd flink opgeknapt was en het nu alweer een poos mis is.

Ik denk dat zoiets goed mogelijk is.

Dit zegt Burrasano over pulsen:

ADVANCED TREATMENT OPTIONS

PULSE THERAPY consists of administering antibiotics (usually parenteral ones) two to four days in a row per week. This allows for several advantages: * Dosages are doubled (ie: cefotaxime, 12 g daily), increasing efficacy * More toxic medications can be used with increased safety (ie: vancomycin) * May be effective when conventional, daily regimens have failed. * IV access may be easier or more tolerable * More agreeable lifestyle for the patient * Often less costly than daily regimens

Note that this type of treatment is expected to continue for a minimum of ten weeks, and often must continue beyond twenty weeks. The efficacy of this regimen is based on the fact that it takes 48 to 72 hours of continuous bactericidal antibiotic levels to kill the spirochete, yet it will take longer than the four to five days between pulses for the spirochetes to recover. As with all Lyme treatments, specific dosing and scheduling must be tailored to the individual patient's clinical picture based upon the treating physician's best clinical judgment.

http://www.ilads.org/lyme/B_guidelines_12_17_08.pdf

[Henriëtte]

Dr. Zhang presentation; drugs targeting borrelia percisters;

https://www.reddit.com/r/Lyme/comments/ ... _possible/

Henriëtte

[Sproetje]

Interessant,
Hij zegt vanaf ongeveer 19:10

Door xenodiagnose kan er soms een organisme in de teek terug worden gevonden.

En:

Na antibioticum kan de borrelia niet meer gevonden worden via op cultuur zetten

Combinatie ab met een antipersister
(Vanaf 1:16:26 )

En hij zegt ook, als ik het tenminste goed heb begrepen dat de proeven mbt het pulsen:
54 dagen aan 1 stuk ab en dan stoppen met alles, totdat alle ab uit het lichaam is.
4 keer pulsen zou genoeg zijn...

Daptomycine zou werkzaer zijn tegen de ronde vormen dan tinidazol

[Henriëtte]

Inflammatory spirochetes debris left behind following antibiotic treatment

The authors also addressed the possibility that the deposits are really biofilms, which generally resist killing by antibiotics. Biofilms are believed to be populated by persister cells, which are in a nondividing state that allows bacteria to tolerate antibiotics. According to the authors, if the deposits had harbored persister cells, those cells should have resumed growing when conditions became favorable for growth again. Because the skin and joints from the treated mice were culture negative and because the skin also tested negative by xenodiagnosis and transplantation assays, the authors quickly dismissed the biofilm hypothesis.

Stricly speaking, the authors are correct. Persister cells should start multiplying again in fresh culture medium. However, it's hard to dismiss the biofilm hypothesis completely given the known examples of culture-negative chronic infections associated with biofilms (see this review for one example). Electron microscopy of the joint tissue could reveal whether these deposits are intact spirochetes or debris.

http://spirochetesunwound.blogspot.nl/2 ... -left.html

Henriëtte

[Sproetje]

Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice
Emir Hodzic , Denise Imai, Sunlian Feng, Stephen W. Barthold
23 Januari 2014

http://journals.plos.org/plosone/articl ... ne.0086907

Abstract
The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.

[Henriëtte]

Persister cells still a problem for Lyme disease patients;

Bacterial persistence is not a new concept. “The term “bacterial persistence” is used to describe the ability of pathogenic bacteria (“persisters”) to survive in infected host tissues despite the presence of effective levels of antimicrobials and antibacterial cellular and humoral immunity,” writes Cabello from New York Medical College in the journal Environmental Microbiology.

http://danielcameronmd.com/persister-ce ... -patients/

Henriëtte

[Henriëtte]

Lyme disease: the promise of Big Data, companion diagnostics and precision medicine;

B. burgdorferi is a relatively complex organism. The spirochete contains enzymes that facilitate tissue penetration and has the ability to form cystic structures and hide in biofilms.29–34 These properties allow the organism to persist in a variety of tissues and hostile environments and escape the reach of antibiotics. The ability of B. burgdorferi to infect privileged sites, such as the eye, synovium, and brain, may also contribute to persistence of the spirochete in human tissues, much like the agents of syphilis, tuberculosis, and HIV/AIDS.1,2 Recent studies have shown that B. burgdorferi forms persister cells that can survive treatment with conventional antibiotics.35,36 The existence of these persister cells supports the view that CLD is associated with persistent spirochetal infection that requires more effective therapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024771/

Henriëtte

[Henriëtte]

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease; 14-4-2018

One viewpoint claims that persistent Lyme disease symptoms are related to ongoing spirochetal infection despite antibiotic therapy. This scenario has been demonstrated in animal models including rodents, dogs and horses using various detection methods [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36], and a recent study in non-human primates showing “persistent, intact, metabolically-active B. burgdorferi after antibiotic treatment of disseminated infection” offers the strongest support for this pathogenesis [37]. Furthermore, comparable studies have suggested persistent infection after antibiotic therapy as a cause of chronic symptoms in humans [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60]. The opposing viewpoint claims that persistent Lyme disease symptoms may be due to spirochetal “debris” without active infection. While a number of studies from Europe and the USA have demonstrated persistence of Bb DNA or antigens in human bodily tissues or fluids, very few studies have demonstrated culture of live Borrelia spirochetes, the highest form of evidence for persistent infection in chronic Lyme disease patients

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023324/

Henriëtte

[Henriëtte]

De Borrelia burgdorferi (Bb) bacterie is een zeer complex organisme en beschikt over een groot repertoire aan overlevings- en aanpassingsmechanismen. Uit onderzoek blijkt dat de bacterie naast de normale beweeglijke spirocheetvorm verschillende andere vormen aan kan nemen, zoals de cystevormen en L-vormen. Er zijn sterke aanwijzingen dat de bacterie in deze vormen langdurig, zonder te delen, in het lichaam aanwezig kan blijven en zo antibioticatherapie kan ontwijken, die zich richt op de zich delende spirocheetvorm van bacteriën. De kennis op dit gebied vertoont nog veel lacunes. Er blijken vele stammen van deze bacterie te bestaan. De bekendste ziekteverwekkende stammen zijn: Bb sensu stricto, Bb garinii, Bb afzelii. Er zijn aanwijzingen dat ook andere stammen van Bb ziekteverschijnselen kunnen veroorzaken (onder andere Borrelia Spielmani, Borrelia lusitaniae, Borrelia bissettii). Van elke stam zijn ook weer substammen bekend, zodat er wereldwijd wel driehonderd stammen en substammen zijn die verschillen in hun eigenschappen. Hierdoor is het moeilijk ze allemaal met eenzelfde test aan te tonen. De verschijningsvormen van deze stammen en reacties op behandeling kunnen verschillen.

https://lymevereniging.nl/lyme/

Henriëtte

[Henriëtte]

Strategies for combating persister cell and biofilm infections;

These stressed cells enter a resting state known as persistence in which they become tolerant to nearly all antibiotics without undergoing genetic change. These dormant cells survive courses of antibiotics, as antibiotics are most effective against actively metabolizing cells, and reconstitute infections. In humans, most of these bacterial infections occur in biofilms in which bacteria attach to one another via secreted proteins, polysaccharides and even DNA. Herein, biotechnological methods are described to combat persister cells and to eradicate biofilms by understanding the genetic basis of both phenomena.

Furthermore, the cost of all biofilm/persister infections to society is substantial; for example, 17 million new biofilm infections occur every year in the United States, and of these infections, 550 000 people die (

Persister cells survive the stress of antibiotic treatment due to their lack of metabolism, rather than through genetic change, as shown via four seminal experiments conducted by the discoverers of the phenotype (Hobby et al., 1942; Bigger, 1944); later, once the antibiotic is removed, the cells can reconstitute infections. Subsequent research corroborated that persister cells are metabolically inactive;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609227/

Henriëtte