Brorson's observation in this paper, that it takes old cysts 4 weeks to convert to as many as 5 mobile spirochetes per cyst, may thus explain the clinically observed 4- week CYCLICITY in Lyme borreliosis (LB) - as well as the observed RELATIVE RESISTANCE to beta-laktam antibiotics, and SERONEGATIVITY !! - and it also explains the clinical observation, that in early LB of only 1-3 weeks duration (only young cysts), shorter antibiotic courses of 10-14 days duration may just about be effective in preventing relapses, while antibiotic treatment of late LB (old cysts) teoretically must be of at least 4 weeks duration, because one must treat long enough for all the oldest cysts to convert back to spirochetes and build their cell walls and thus be susceptible to a beta-laktam-antibiotic!!
A rapid method for generating cystic forms of Borrelia burgdorferi, and their reversal to mobile spirochetes. Brorson O, Brorson SH "Excerpt from discussion section:
The cysts observed in our study seem to resemble the spheroplast-L-forms observed by other researchers (11, 35), which seem to have defects
in their cell wall manifested by resistance towards beta-lactam antibiotics (16). Since the conversion from normal mobile spirochetes to
cystic forms occurred very rapidly, complete absence of cell wall as in L-forms is dubious, but the similarity with L-forms is shown by the
inability to retain their original shape. The biological activity of the cystic forms was confirmed by the step by step development to
normal mobile spirochetes in BSK-H medium, and also indicated by the presence of RNA in 5-week-old cysts due to red-orange staining with
acridine orange (pH 6.4) (Fig. 4b). This seems to be a new observation in the development of B. burgdorferi (20). Bruck et al. (35) also illustrated biological activity by incorporation
or S-methionine in the cysts (spheroplast). The creation of as many as five spirochetes from each cyst may explain why the generation time was
shorter for production of mobile spirochetes from cysts compared to that for normal mobile spirochetes cultivated conventionally. The
generation of the normal mobile spirochetes which were converted from cysts was somewhat variable in the sense that they sometimes seemed to need a
long stationary period before exponential growth occurred. Whether cysts are converted to normal mobile spirochetes or not depends strongly on the
growth medium used, and possibly also the generation time. It seems as though normal mobile spirochetes are developed from the dense core structures or the
cyst by being ""fed"" with core substances as the ""infant-spirochete"" protrudes from the cyst. The development of vegetative bacteria from dense
L-forms has been suggested as a method for Enterococcus faecalis to convert from L-forms to vegetative forms (40). The observation by TEM
that blebs transformed into thin filaments leads us to speculate that these filaments develop to normal mobile spirochetes. If so, the blebs have
to contain enough genetic material to synthesize a new bacterium (22). Old cystic forms of B. burgdorferi require
prolonged cultivation to convert to normal mobile spirochetes (4 weeks as opposed to 9 days for young cysts). Similar cystic forms may occur in
the human organism (11, 14, 15), and they may explain the long periods or latency, resistance to antibiotics, negative serological results
(3-7, 10, 12, 13, 25), and low PCR sensitivity (5, 8, 10). For these reasons it is important to examine the antigens of the envelope of the
cysts. DNA sequences for PCR analysis, and the cysts sensitivity to antibiotics and other chemicals. It may be hypothesized that antigenic
variation in B. burgdorferi (19, 41) occurs inside the cyst while the microbe is protected against external stress, and therefore antigens
detected on the cyst envelope in vitro differ from the ones present in vivo. In conclusion, we believe that the present method for rapid and
easy generation of stable cysts will be a useful tool in further research on B. burgdorferi."
Posted by Pinelady (Member # 18524) on :
This is pretty neat. My current Lyme doc, when I previously showed him an article by the same researchers concerning Tindamax, said that not only was he familiar with their work, but that he knew them.
The Tindamax seemed to have helped me by the way.
Posted by MariaA (Member # 9128) on :
Start where it says: "inhibition of PKCB2 activation..."
Posted by Dawn in VA (Member # 9693) on :
Interesting info indeed.
Posted by jl123 (Member # 15594) on :
I am confused why aren't more lyme patients not at least a little exited by this discovery?
It seems that Tygecycline might be different than other anti-bacterials in that the lyme bugs can't run away/drill away or shape-shift like they can with most other medicines? No?
So if this drug kills each bug on contact no matter the bugs "reaction" then its doing more than other drugs know to this point?
Does anyone have any idea when this drug might start human lyme trials? thanks, J
Posted by KS (Member # 12549) on :
This is very interesting...
Posted by treepatrol (Member # 4117) on :
up
Posted by Marnie (Member # 773) on :
Must REACH the pathogen first.
This MIGHT be at play:
"Impaired microvascular circulation hinders white cell migration into the area of infection and limits the ability of antibiotics to reach the site of infection in an effective concentration."
Which makes it harder, not impossible, but harder.
Posted by Pinelady (Member # 18524) on :
JL I think with the excitement comes fear.
There have been a few antibiotics introduced to the
market and quickly withdrawn due to incidence of
adverse effects in some individuals.
Horrible I might add, most noted in patients who have socalled autoimmunity/ongoing infections of virus' and bacterias'.
So to say this will be acceptable in Lyme patients remains to be seen- but could be!
Posted by David Miller (Member # 21583) on :
This isn't for casual or early stage use as there's no oral form available.
It's IV only for now. I wonder if it'll stay that way. Did anyone catch how well it penetrates? Vancomycin is only used for certain gastric infections because it won't cross the intestinal barrier. Hopefully tigecycline isn't so restricted and can be taken orally before too long.
Posted by Beachinit (Member # 21040) on :
Speaking of IV tetracycline derivatives (tigecycline) in place of orals, how does that compare to say IV azithromycin in place of oral macrolides. Both target tissue and also get the blood levels higher when given IV. Dr. B's handout seemed to speak well of IV zithro. Have the Brorsons already tested zithro? I have heard zithro is cheaper (for drug not including administration etc) IV than tablet form.