Re: resistance of Bb variants

[Guest guest]

,

You can click on the "fulltext" box to read the whole article which is short but you might want to follow up the references they give including:

Kersten A, Poitschek S, Rauch S, Aberer E (1995) Effects of penicillin,

ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi.

Antimicrob Agents Chemother 39:1127–1133

Nelly

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15248163 & query_hl=5

Int Microbiol. 2004 Jun;7(2):139-42.

Related Articles,

Links

An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole.Brorson O, Brorson SH.Department of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway.

(...)

Fourteen days of treatment with penicillin, doxycyclin or

ceftriaxone is often believed to cure the infection, but all

commonly used antibiotics have their shortcomings, and the

frequency of relapses may be highly dependent on the chosen

treatment and the phase of the disease [23−26]. A study of

cytomorphic variations of B. burgdorferi isolates from

patients with or without antibiotic treatment showed that

penicillin can induce membrane-derived vesicles (cysts or

spheroblast L-forms) in vivo [27]. This conversion of mobile

Borrelia to cystic forms was subsequently observed for ceftriaxone,

doxycyclin [17], ciprofloxacin [18] and vancomycin

[12] at concentrations achievable in vivo. The fact that B.

burgdorferi has the ability to convert (and reconvert) to cystic

forms both in vivo and in vitro [1,4−6,10,14,15,21,27,28]

may be regarded as an explanation why the infection may be

persistent and reactivate. Therefore, it is reasonable to suggest

that all germinative forms of the bacterium (and not only

the motile form) should be destroyed so that Lyme borreliosis

can be treated effectively. The aim of this study was to

investigate the susceptibility of motile and cystic forms of B.

burgdorferi to the second-generation amidazole tinidazole.

[infections] resistance of Bb variants

Nelly I've spent some time looking for work showing non-helical Bb forms to be resistant, but havent been able to locate it. Theres that one by (I think) Aberer showing that more cysts etc formed in vitro in response to ceftriaxone (as opposed to non-B-lactam drugs), but that experiment was only 2 days long. I dont think it was made clear whether or not the ongoing presence of ceftriaxone would have prevented those variant forms from multiplying, or whether any forms would be able to multiply in the presence of tetracyclines, etc. The Jemsek Clinic treatment guidelines are referenced, yet they do not reference their statement that the non-helical forms have broad intrinsic resistance.Klempner famously showed that the presence of host cells protected Bb from eradication by high-dose ceftriaxone in vitro. But the mechanism for that was not investigated, and other workers found that protein-synth-inhibiting drugs did eradicate Bb from some sort of host cell culture.I looked for refs on this idea in some of the Brorson papers but cant recall whether I finished. Anyways I didnt find anything so far.So basically I havent seen anything showing that transformation into nonhelical forms averts bacteriostasis, ie allows ongoing reproduction in the presence of abx. If you or anyone can tip me off about any such experiment I'd head to the library extremely immediately.I havent got around to significant study on the sequestered anatomical sites problem yet, but hope to someday. > ,> > Bb Cysts, blebs, granules? The Brorsons' studies etc Plenty to show that spiros do have mechanisms to ensure survival under "adverse circumstances" ie in the presence of most abx in-vitro. They can then be "reborn" from their mutated forms. > > In-vivo they also "flagelate" their way to sequestered sites very quickly and from there they can re-circulate and repopulate whenever they choose to. > > But of course that's only hearsay, since me, myself, personally have not got my own equipment in my backroom where I can play microbiologist and then scream at people that what "I don't see(or don't know enough about!) can't "possably"(sic) make you sick".> > Nelly > >

[Guest guest]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=14560706 & query_hl=5

Neurol Neurochir Pol. 2003;37 Suppl 2:29-38.

[Pathogenetic-clinical problems of Lyme borreliosis][Article in Polish]Hermanowska-Szpakowicz T, Zajkowska JM, Pancewicz SA, Kondrusik M, Grygorczuk SS, Swierzbinska R.Kliniki Chorob Zakaznych i Neuroinfekcji, AM w Bialymstoku.In this article a short review of pathogenesis and clinical manifestations of Lyme disease is presented. As regards pathogenesis, attention was paid to the mosaic protein structure of the B. burgdorfieri spirochete, particularly of outer surface proteins (Osp) that influence the clinical course and diagnosis of the disease. The presence of various atypical spirochete forms: spheroplastic L (without cell walls), cystic, and granular "blebs" may lead to a chronic form of the disease and to a low efficacy of antibiotic therapy. An important part of the pathogenesis is epithelial damage, stimulating the production of inflammatory cytokines (mainly IL-1, TNF-alpha, IFN-gamma), adhesive molecules and acute-phase proteins. Moreover, in the course of the disease not only an impairment of phagocytosis and chemotaxis was found, but also B. burgdorfieri spirochete binding by antibodies into immunological complexes that may maintain chronic inflammation. In terms of the Asbrink classification, complaints predominating in the clinical picture of an early and late stage of the disease were presented, with an emphasis on neuroborreliosis.Publication Types:

ReviewPMID: 14560706 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=14961976 & query_hl=5

APMIS. 2004 Jan;112(1):57-62.

Induction of cystic forms by different stress conditions in Borrelia burgdorferi.Murgia R, Cinco M.Spirochete Laboratory, Dipartimento di Scienze Biomediche, Universita' degli Studi di Trieste, Via Fleming 22, 34127 Trieste, Italy. rmurgia@...Cystic forms of Borrelia burgdorferi might represent a low metabolic activity state or phase of B. burgdorferi cells that allows the spirochete to survive in a hostile environment until conditions are favourable to multiply again. In this study we evaluated the rate of cyst formation induced by oxidative stress, pH variations, and heating, reconversion of cysts to vegetative forms, and some aspects of their metabolic activity. We observed cyst formation in the presence of extreme pH values, and at high temperature, but the best production of cystic forms was observed in the presence of H2O2. When transferred to BSK II medium, the cystic forms reconverted to spirochetes in relation to their age and type of induction treatment. Furthermore, we demonstrated a low metabolic activity of cystic forms by measuring amino acid incorporation. *****Overall, these data suggest that the phenomenon of conversion to cysts by B. burgdorferi provides a limited survival potential. This short-term survival, however, gives borreliae an additional chance to overcome unfavourable environmental conditions.PMID: 14961976 [PubMed - indexed for MEDLINE]

2002 Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role Wiener Klinische Wochenschrift, 114(13-14):574-9.

Piazzetta C; of RpoS. Cinco M.

[Abstract:] “It has been demonstrated recently that cells of Borrelia burgdorferi sensu lato, the etiological agent of Lyme disease, transform from mobile spirochetes

into nonmotile cystic forms in the presence of certain unfavourable conditions, and that cystic forms are able to reconvert to vegetative spirochetes in vitro and in vivo.

The purpose of this study was to investigate the kinetics of conversion of borreliae to cysts in different stress conditions such as starvation media or the presence of

different antibiotics. Using the same experimental conditions we also investigated the possible role in cyst formation of RpoS, an alternative sigma factor that controls

a regulon in response to starvation and transition to stationary phase. We observed that beta-lactams penicillin G and ceftriaxone, the antibiotics of choice in Lyme

borreliosis treatment, favoured the production of cysts when used with serum-depleted BSK medium. In contrast, we observed a low level of cyst formation in the

presence of macrolides and tetracyclines. In order to elucidate the role of the rpoS gene in cyst formation we analyzed the reaction of the rpoS mutant strain in

comparison with its wild-type in different conditions. Under the same stimuli, both the wild-type borrelia and the rpoS knock-out isogenic strain produced cystic forms

with similar kinetics, thus excluding the participation of the gene in this phenomenon. Our findings suggest that cyst formation is mainly due to a physical-chemical

rearrangement of the outer membrane of Borrelia burgdorferi sensu lato leading to membrane fusion and controlled by different regulation mechanisms.”

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=10052721 & query_hl=2

APMIS. 1998 Dec;106(12):1131-41.

A rapid method for generating cystic forms of Borrelia burgdorferi, and their reversal to mobile spirochetes.Brorson O, Brorson SH.Department of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway.Mobile Borrelia burgdorferi were transferred to distilled water (10(6) per ml). The cultures were observed by dark field microscopy (DFM), interference contrast microscopy (ICM) and transmission electron microscopy (TEM). 95% of the spirochetes were converted to cysts after 1 min, and after 4 h no normal mobile borreliae were observed. When transferred to growth medium (BSK-H), the cysts became smaller and more irregular, and were filled with organic substances. After 1 day, 1-5 thin structures sprouted from the cysts. They continued to grow in both length and thickness until they attained a normal spirochetal structure. Finally, these new-born spirochetes detached from the cysts, by which time their mobility had become normal. The present method for producing large amounts of cystic forms of B. burgdorferi is well suited for further studies of this unique microbe.PMID: 10052721 [PubMed - indexed for MEDLINE]

[infections] resistance of Bb variants

Nelly I've spent some time looking for work showing non-helical Bb forms to be resistant, but havent been able to locate it. Theres that one by (I think) Aberer showing that more cysts etc formed in vitro in response to ceftriaxone (as opposed to non-B-lactam drugs), but that experiment was only 2 days long. I dont think it was made clear whether or not the ongoing presence of ceftriaxone would have prevented those variant forms from multiplying, or whether any forms would be able to multiply in the presence of tetracyclines, etc. The Jemsek Clinic treatment guidelines are referenced, yet they do not reference their statement that the non-helical forms have broad intrinsic resistance.Klempner famously showed that the presence of host cells protected Bb from eradication by high-dose ceftriaxone in vitro. But the mechanism for that was not investigated, and other workers found that protein-synth-inhibiting drugs did eradicate Bb from some sort of host cell culture.I looked for refs on this idea in some of the Brorson papers but cant recall whether I finished. Anyways I didnt find anything so far.So basically I havent seen anything showing that transformation into nonhelical forms averts bacteriostasis, ie allows ongoing reproduction in the presence of abx. If you or anyone can tip me off about any such experiment I'd head to the library extremely immediately.I havent got around to significant study on the sequestered anatomical sites problem yet, but hope to someday. > ,> > Bb Cysts, blebs, granules? The Brorsons' studies etc Plenty to show that spiros do have mechanisms to ensure survival under "adverse circumstances" ie in the presence of most abx in-vitro. They can then be "reborn" from their mutated forms. > > In-vivo they also "flagelate" their way to sequestered sites very quickly and from there they can re-circulate and repopulate whenever they choose to. > > But of course that's only hearsay, since me, myself, personally have not got my own equipment in my backroom where I can play microbiologist and then scream at people that what "I don't see(or don't know enough about!) can't "possably"(sic) make you sick".> > Nelly > >