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Chlamydiae have a biphasic life-cycle. A small, infectious, non-replicating extracellular particle (the elementary body, or EB) spreads the infection both between persons and between host cells. On gaining entry to a host cell, the EB is able to transmute into a larger, diffuse form (the reticulate body, or RB) which utilises the host cell’s energy-generating organelles for its own use. It is an energy-parasite. By this means it is able to replicate rapidly, releasing multitudes of EBs into the extracellular milieu. Agents which block protein synthesis, such as doxycycline and roxithromycin, stall this replicating phase, but do not eliminate the intracellular organism.

Chlamydiae are complex organisms. Long ago their ancestors must once have been free-living. They must have possessed their own energy-generating pathways. The transformation from EB to RB is an active change, and an active change implies the retention of at least some of these pathways. The ones with the most utility for this purpose would be anaerobic, and thus susceptible to metronidazole. Metronidazole should kill the organism while it transformed itself from the EB to the RB.

During the unique chlamydial life cycle, it is known that metabolically-inactive spore-like EBs are released into the extracellular milieu. Although these released EBs are infectious, they may not immediately infect nearby susceptible host cells until appropriate conditions for EB infectivity are present. The result of this delay in infection is the extracellular accumulation of metabolically-inactive, yet infectious, EBs. This produces a second type of chlamydial persistance referred to herein as EB "tissue/blood load"). This term is similar in concept to HIV load and is defined herein as the number of infectious EBs that reside in the extracellular milieu. Direct microscopic visualization techniques, tissue cell cultures, and polymerase chain reaction test methods have demonstrated that infectious EBs are frequently found in the blood of apparently healthy humans and animals. This phenomenon is clearly of great clinical importance in chlamydial infections as these metabolically-inactive EBs escape the action of current antichlamydial therapy which is directed only against the replicating intracellular forms of Chlamydia. The presence of infectious extracellular EBs after the completion of short term. anti-replicating phase therapy for chlamydial infections has been shown to result in intracellular infection relapse

Doxycycline and roxithromycin block the replicating phase and may be expected to force the organism to maintain itself by using its own primitive anaerobic respiratory mechanisms. In this suspended state it would be susceptible to anti-anaerobic agents such as metronidazole.

As described in previous sections. it is also believed that persistance of chlamydial infections, in part, may be due to the presence of cryptic forms of Chlamydia within the cells. This cryptic intracellular chlamydial form apparently can be activated by certain host factors such as cortisone (Yang et al., Infection and Immunity, 39:655-658 (1983); and Malinverni et al., The Journal of Infectious Diseases, 172:593-594 (1995)). Antichlamydial therapy for chronic Chlamydia infections must be continued until any intracellular EBs or other intracellular cryptic forms have been activated and extracellular EBs have infected host cells. This reactivation/reinfection by chlamydial EBs clearly is undesirable as it prolongs the therapy of chlamydial infections, as well as increases the opportunity for antimicrobial resistance to occur.


Physiochemical agents have been identified that can inactivate chlamydial EBs in their respective hosts by reducing disulfide bonds which maintain the integrity of the outer membrane proteins of the EBs. For Chlamydia, disruption of the outer membrane proteins of EBs thereby initiates the transition of the EB form to the RB form. When this occurs in the acellular milieu where there is no available energy source, the nascent RB perishes or falls victim to the immune system. Thus, disulfide reducing agents that can interfere with this process are suitable as compounds for eliminating EBs.

One such class of disulfide reducing agents are thiol-disulfide exchange agents. Examples of these include, but are not limited to, 2,3-dimercaptosuccinic acid (DMSA; also referred to herein as "succimer"); D,L,-.beta.,.beta.-dimethylcysteine (also known as penicillamine); .beta.-lactam agents (e.g., penicillins, penicillin G, ampicillin and amoxicillin, which produce penicillamine as a degradation product), cycloserine, dithiotreitol, mercaptoethylamine (e.g., mesna, cysteiamine, dimercaptol), N-acetylcysteine, tiopronin, and glutathione. A particularly effective extracellular antichlamydial agent within this class is DMSA which is a chelating agent having four ionizable hydrogens and two highly charged carboxyl groups which prevent its relative passage through human cell membranes. DMSA thus remains in the extracellular fluid where it can readily encounter extracellular EBs. The two thiol (sulfhydryl) groups on the succimer molecule (DMSA) are able to reduce disulfide bonds in the MOMP of EBs located in the extracellular milieu

Hi Daunted,


Can you tell me which combination are you taking with amoxicilin and what are the doses in mg.Because i have ppms my bacteria load is huge and i still have too much RB form of bacteria in my body, after clearing RB forms from my body i might switch to amoxicilin combination to manage extracellular EB forms which i must have alot in my body.


Take care,

Guner

Hi Daunted,


Can you tell me which combination are you taking with amoxicilin and what are the doses in mg.Because i have ppms my bacteria load is huge and i still have too much RB form of bacteria in my body, after clearing RB forms from my body i might switch to amoxicilin combination to manage extracellular EB forms which i must have alot in my body.


Take care,

Guner