Jaep -

[Guest guest]

Ah yes, smart combo application gets significant milage out of a drug

that could easily be dismissed as too toxic to be useful. A smooth move.

If bacterial persistence underlies most of our illnesses, as I

personally consider fairly probable, the reasons for refractoriness to

abx may not be mutational resistance. Which is where the bacterium has

a mutation in the drug target molecule that prevents the drug from

binding its target, or the bacterium upregulates a membrane pump that

pumps out the drug (or downregs an intake pump), etc.

Or a bacterium can just be dormant and stop taking in molecules,

including drugs, from its millieu for a while (indefinitely).

Matt once showed me this paper, which is also referenced by Wheldon in

his paper on MS. It may demonstrate resistance reflecting none of

those mechanisms, but rather soemthing we just dont understand:

http://circ.ahajournals.org/cgi/content/full/103/3/351

I cant figure out whether that paper is saying the abx-refractory Cpn

infection of monocytes is productive, or is non-productive. It seems

to possibly vaguely contradict itself on that. A non-productive

" bunker " does not look like a great candidate for a place where a

abx-refractory infection can draw strength. If the bacteria dont

replicate, they should slowly die out.

However, this finding seems to say Cpn can *productively* infect

lymphocytes, and be refractory to abx there:

http://aac.asm.org/cgi/content/full/47/6/1972

So like, WHY? Or more accurately, HOW the heck does this happen with

Cpn, and could it happen with some other organisms. No ideas come to

mind. Its pretty damn weird.

The Wirostko/ group visualized L-form " non-infectious uveitis "

bacteria within monocytes, neutrophils, and lymphocytes (and

endothelial and epithelial cells).

<Jaep@L...> wrote:

> Thanks , I don't grasp the mechanism either, I think & talk in

> principles , I don't think many if any have an intimate knowledge of

how the

> IS works , I see the problem with mono therapy [tetracylines

probably wont

> ever fly] that's why drug combos are so much more effective ,

especially

> if the drugs involved work in different ways ...Take a look at this

article

> ..its a very convincing picture on combos ..the pity is the work is not

> taken up if you like ..its not adopted for further study ...its just one

> more piece of information in a sea of information ...we need a good

> co-ordinator...

>