Barb - Cpn invulnerable in leukocytes

[Guest guest]

Hi Barb,

Yeah it seems most people think the leukocytes can be

transporters... I remember reading some disagreement about it but

maybe its pretty much proved by now. Still, the leukocyte could be a

transporter, and a productive infection site, and a " bunker " where

abx are ineffective for mysterious reasons - all at the same time.

My thinking is, for an infection to always relapse after appropriate

abx, there must be a bunker (or else a set of dormant bacteria, or

resistant mutants). For an infection to not fully respond to long-

term appropriate abx in the first place, there must be a bunker

which is also simulataneously a site that permits bacterial growth.

I'm really glad chlamydia are getting so much attention these years

as chronic infectors.

I didnt find anything too confusing in the 2nd paper, but in the

first paper I was a little confused about whats up. My best

interpretation is that the elementary bodies are phagocytosed by the

primary monocytes, differentiate to retiuclate bodies and multiply

limitedly(?), then stop(?) multiplying but remain metabolically

active.

During the 10 days of the experiment, the monocytes didnt lyse, so

its hard to see how Cpn would get out of monocytes and disperse if

they were in a host. If I'm not mistaken they need to change back to

elementary bodies before exposing themselves to the host humor (the

elementary form doesnt replicate, and the reticulate form does not

infect cells).

I think a normal chlamydial life-cycle in epithelial/endothelial

cell culture with staurosporine (to make the host cells more

vulnerable) is like 2-5 days... so maybe if the experiment were 30

days long, we would see the monocytes eventually lysed by the Cpn

after they transformed to EBs, as is usual. They might just need

more time cause of slower growth in monocytes. Unfortunately, as I

say, I dont feel sure from the paper whether they totally stopped

replicating at some point, or not.

Or, just conceivably, Cpn might be able to escape a monocyte without

lysing it - something I dont think any bacterium is known to do,

ever. In that case the cell could become a permanent bacteria

factory.

Or Cpn might escape by surviving the apoptosis of the monocyte.

Frustratingly, Ive seen so many authors casually refer to

intracellular pathogens either being able to survive apoptosis

sometimes, or NOT being able to survive apoptosis essentially ever,

but there is never any detail or reference to any experiment! So I

have no idea. Argh. I think I read Mtb can survive it tho, at a

certain rate.

Or, possibly, Cpn cant escape a monocyte after all.

Bacteria suck. And as you say, these stealth bacteria are hard to

visualize - and when someone does it, like the Wirostko/

group did so well, their work does not inspire the appropriate

frenzy or at least wave of followup investigation.

Till we visualize these germs its pretty hard to figure out how they

evade abx in some unknown way, assuming that is the case. These

papers on Cpn, especially the 2nd one, seem to demonstrate such an

unknown way of resistance even during growth. Its tantalizing.

<egroups1bp@y...> wrote:

>

> :

>

> I don't think the monocytes were used as 'bunkers' -

> they were used as c.pneumonia " transportation services " from the

> lungs to other organs.!! I would view this as a porductive move

for

> the bacteria - get's it safely from one organ to another - and

> because it's intracellular- hard to kill.

>

> I don't find the second paper you cite contradictory- as they

state

>

> QUOTE:

> The study reported here clearly demonstrated that the

susceptibility

> of C. pneumoniae to antibiotics was dependent on host cells, even

> though the results were obtained under only limited experimental

> conditions. The growth of C. pneumoniae in HEp-2 epithelial cells

was

> markedly suppressed by the antibiotics used, and MICs and MBCs

were

> comparable to those in previous reports (11, 16, 26). In contrast,

> bacterial growth in THP-1 monocytes and Molt 4 T lymphocytes did

not

> show uniform susceptibility to the antibiotics used. END QUOTE

>

> And we certainly know that the intracellular pathogens (or stealth-

> or occult pathogens) are hard to find- hard to erradicate.

> Barb

>

>

>

> > > 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...

> > >