Cpn Theory: Cpn Metabolism
Cpni Theory: Cpn Metabolism
Chlamydia Pneumonia is an obligate intracellulari pathogen that relies on the host cell for energy. It is able to obtain energy through multiple mechanisms. The primary mechanism is exchanging ATP for ADP with the host cell mitochondria. ATP and ADP are exchanged using a proton pump which may require a lower chlamydial pH than that of the host cell. Probably the use of protons to exchange ATP for ADP and the subsequent use of ATP lead to a homeostasis of Cpn pH so this should be able continue under normal circumstances. This pH level and reliance on ATP/ADP exchange probably represents the reticulate body phase in chlamydial development. At this pH level Cpn can probably make the proteins needed for replication.
When stressed Cpn may need to supplement ATP/ADP exchange with additional energy sources such as glycolysis (anaerobic fermentation to lactic acid) and amino acid catabolism (with an ammonia byproduct). The pathway that is chosen would be based upon host cell resource availability although presumably glycolysis dominates as that is the case in most cells and bacteria. If glucose or pyruvate is abundant it is probable that glycolysis is used for obtaining additional energy. This should efficiently reduce the pH within the Cpn membrane. If the Cpn pHi drops below some thresh hold, Cpn probably begin making proteins and enzymes needed to convert to the elementary body state. So "stressing" Cpn with adequate glucose or pyruvate should result in Cpn converting to an elementary body.
If glucose or pyruvate stores are limited, Cpn may obtain energy from amino acid catabolism which should increase pHi. Once the pH rises to the level of the host cell, Cpn would no longer be able to obtain energy from ATP/ADP exchange. And as the pH continues to rise it may no longer able to make many of the proteins that it normally does to replicate. However some protein synthesis such as production of HSPi-60 probably occur more readily. This higher pH level represents the cryptic state. The pH rise would be limited by a NhaD antiporter. Without the availability of ATP/ADP exchange, Cpn would necessarily have to obtain all of its energy from alternative sources and in cells with chronically low glucose levels, it is unlikely that Cpn would easily exit the cryptic state even if the initial stress is removed.
This may explain some observations surrounding Cpn infections. Cells with modest blood flow such as joints and skin should have lower availability of glucose and generally produce persistent infections. Cells with a very large number of mitochondria might also favor persistence as the mitochondria may compete with Cpn for glucose. Of course conditions in these persistently infected cells would sometimes change. A diet high in sugars, stimulants, or adrenaline release from stress might temporarily elevate the glucose levels in these cells and allow Cpn to return to reticulate body state and begin replicating. Also temporarily lowering the pH of the host cell should lower the pH of the Cpn as they have NhaD antiporters which should cause Cpn's pH to track down with the host cell. Corticosteroids would remove the stress caused by WBC's releasing interferon (and inducing iNOS) while also increasing glucose levels.