thoughts on cryptic bodies: is there evidence for two classes? And have they different properties?
There has been quite a bit of discussion on new strategies of treatment. I thought I should add my two pence.
There are a few conjectures which I would be very pleased to be able to air. I can hear William of Occam in the background, honing that famous razor of his.
Here are my assertions:
a) The naturally occurring Cryptic (NOC) form occurs when chronic host stressors are applied to the Reticulate form.
b) In the NOC, bacterial protein synthesis is not inhibited. Heat Shock Protein genes are upregulated. Excess HSPs are made. HSPs are highly irritant, molecular mimics. This is why the NOC is dangerous. It is certainly not inert.
c) The antibiotic-induced Cryptic (AIC) form occurs when protein-synthesis inhibitors (tetracyclines, macrolides and rifampicin or rifamycins) are given.
d) The AIC is an abnormal form which has a limited ability to produce HSPs. Heavily infected host cells may therefore regain the capacity to undergo systematic cell-death via the caspase route. (This may account for the unpleasant die-off reactions some people get with antibiotics usually considered bacteriostatic.)
e) The AIC will have a limited ability to form actin filaments which steers the endosome away from host lysosomes. The AIC is likely to become depleted over months of bacteriostatic treatment even in host cells which do not undergo apoptosis.
f) NOCs do not seem to be susceptible to Nitroimidazoles. You can give Metronidazole to someone with an obvious large Cpn load, and they get no die-off reaction.
g) AICs are highly susceptible to Nitroimidazoles, in that die off reactions are often severe.
Summarizing, I would say that the evidence points to there being two classes of Cryptic Body. These two classes are radically different. I agree that HSP overproduction plays a huge role in the natural chronic infection with Cpn, but I would find it hard to believe that it becomes more important when treatment is begun. I daresay that pyruvate may well be able to convert the NOC back into the RB form, but I doubt if it could convert the AIC form back into a RB form. The AIC form should be well and truly stalled.
DW:] There, William. I rest my case. Have I multiplied entities without need, or does it escape your razor?
W of O:] Tu me defendas calamo; ego te defendam novaculo!
(Defend me with your pen; I'll defend you with my razor!)
DW:] I knew I could rely on you! I'll buy you a beer this evening!