The Disease State Of Chlamydia Essay, Research Paper

A parasite is defined as an organism that lives in or on another organism, called a host (2). If the parasite has the capacity to cause disease in the host then the parasite is called a pathogen. Disease in the host is caused by the infection of the parasite. The interaction between the host and parasite is complex. Both the pathogen and the host strive for survival in some of the cases. The pathogen divides within or on the host in an attempt to keep its species alive while the host?s defense mechanisms simultaneously attempt to eliminate the pathogen. The extent of the “battle” for survival varies depending on the relationship. This paper discusses the disease state of Chlamydia; how the organism invades its host, evades the host?s defense mechanisms, multiplies within the host, and is released from the host. Certain aspects of the chlamydiae will be compared to the other pathogens, Rickettsia and the Herpesviruses as they relate to the disease state.

Bacteria are classified into four categories according to shared characteristics, these categories are then divided into groups, and the groups are divided further into subgroups. The ninth group of bacteria contains only two subgroups called the Rickettsias and Chlamydias (1). According to 16S r RNA sequencing Rickettsias are related to the purple Bacteria and Chlamydias comprise a major branch of Bacteria (2). Viruses are not grouped among the prokaryotes. In fact viruses are not really organisms by definition. They are genetic elements that are replicated by host cells. The herpesvirus group contains over seventy viruses all of which are potentially pathogenic. Only five of these viruses infect humans. This group of viruses resemble each other and have biological properties in common, particularly the latency-reactivation stages in the disease state.

Before discussing the host-parasite interactions the developmental cycle of chlamydiae need to be mentioned briefly. Chlamydiae alternate between two cell types called elementary bodies and reticulate bodies. The elementary bodies are released from infected host cells and enter uninfected host cells. In the newly infected host cells the elementary bodies transform to reticulate bodies. The reticulate bodies divide in the host cell and then transform themselves into new elementary bodies. The elementary bodies never divide and the reticulate bodies never invade host cells, they are both incapable of doing the other?s “job”.

The morphology and metabolisms of viruses are completely different from that of bacteria. The herpes group of viruses consist of a central core, called a nucleoid, containing the viral DNA. The nucleoid is surrounded by a capsid made of tubular protein subunits called capsomeres. The capsid is surrounded by an envelope coated with viral antigens. Other viruses have variations of this morphology.

In the sense that chlamydiae change form between infecting and multiplying they can be compared to viruses. Viruses have extracellular and intracellular forms. In the extracellular form the virus is in the form described in the previous paragraph. When the virus infects the host cell it leaves behind its capsid and envelope so that only its nucleic acid enters the host cell. The viral nucleic acid is replicated by host cell machinery. So both chlamydiae and viruses, including the herpesviruses, have an extracellular form that attaches to the host cell and an intracellular form that replicates or is replicated in the host cell.

The first step in the host-parasite interaction is the attachment of the parasite to the host cell. Chlamydial cell walls resemble those of gram-negative bacteria except that the chlamydial cell walls lack peptidoglycan. Instead of the peptide cross links in the peptidoglycan layer, disulfide bonds between outer membrane proteins provide rigidity to the wall. Interestingly, rickettsiae also have a gram-negative type of cell wall and they too lack peptidoglycan. The same outer membrane proteins of the chlamydial cell walls have also been reported in the scrub typhus rickettsiae. “It has been suggested [by Hatch et al.,(1981) that] negative chlamydial ligands are neutralized by electrostatic interaction with host ligands, thus leading to the binding of chlamydiae to host cells by powerful van der Waals forces” (3). It is not yet clear whether chlamydiae enter the host cell by means of microfilament-dependent phagocytosis or receptor-mediated endocytosis or if both of these pathways are somehow involved together (3). The major outer membrane protein (MOMP) of the chlamydial cell has been suggested to function as a chlamydial adhesin by promoting the electrostatic and hydrophobic bonding with host cells (3). As the chlamydiae enter the host cell they become enclosed in a membrane bounded vesicle called a phagosome. The phagosome and the chlamydiae within is called an inclusion.

Once inside the host cell there are two possible fates for the chlamydiae or any other invading parasite. One fate is that the parasite is destroyed by host mechanisms for defense and the other is that the parasite evades the host mechanisms and multiplies. One mechanism of host defense against parasites is the fusion of their lysosomes with parasite-containing phagosomes followed by the release of acid hydrolases into the phagosome to destroy the parasites. Chlamydiae have the ability to avoid lysosomal fusion. The lysosomes in the cell do not fuse with the inclusions. It is not known yet how this is possible. The rickettsiae escape from the phagosome before lysosomal fusion. Upon entering the host cell the chlamydial elementary bodies begin to reorganize into reticulate bodies.

“Chlamydial multiplication is the product of structural and metabolic interactions between chlamydiae and host cells” (3). The elementary bodies within the inclusions transform into reticulate bodies by undergoing numerous morphological intermediate stages. There is an enormous increase in size. The reticulate body is ten to one hundred times larger than the elementary body. There are also changes in the structure of the cell was and the nucleoid. Multiplication occurs in the inclusions by binary fission of the reticulate bodies. Some of the reticulate bodies transform to elementary bodies while others remain reticulate bodies and continue dividing. The inclusion membrane enlarges to accommodate the newly synthesized cells. The inclusion membrane is extremely stable, capable of accommodating several hundred reticulate bodies, elementary bodies, and intermediate bodies.

All of the energy that the chlamydiae use for growth comes from the host cell. This is an interesting feature of the chlamydial-host interaction that is also seen in rickettsial-host interactions. The host cell contains ATP-ADP translocases which are enzymes in adenylate nucleotide transport systems. These enzymes were discovered in mitochondria and chloroplasts by Viginais et. al. (1985). Normally these translocases couple the excretion of ATP, into the cytoplasm, with the uptake of ADP, into the organelle, across the mitochondria or chloroplast membrane. However, translocase activity in the presence of these intracellular parasites is reversed, ATP is taken in, to the inclusion, and ADP is excreted, out of the inclusion, across the inclusion membrane.

Translocase activity in intracellular parasites was first demonstrated in R. prowazekii by Winkler (1976). Within host cells the rickettsiae received ATP from their host by exchanging an ADP for it, but if the host ATP was unavailable the rickettsiae would make the ATP on their own. Chlamydiae exchange ADP for host ATP just as the rickettsiae but they are unable to synthesize their own ATP. Viruses, including the Herpesvirus have no metabolic capacity of their own, they must always use host machinery to get energy and for the synthesis of all their macromolecules.

The developmental cycle ends with the release of the chlamydiae from the host cell. Several modes of release have been proposed but it is unclear what actually happens (3). One mode of release is lysis of the host cells followed by the release of the chlamydiae. In this mode of release the inclusions burst inside the host cell, disrupting host cellular organelles. Another mechanism of release “in some host cells is as follows; the inclusion is extruded through a focal distention of the cytoplasmic membrane of the host cell without apparently affecting the rest of the cell surface” (3). Here the host cell continues its normal functions and is not destroyed. The inclusion must somehow be opened outside of the cell, possible by lysis caused by the growing bodies within it. In both cases there is no preferential release of elementary bodies and reticulate bodies and intermediate bodies are also released at the same time. At this point the elementary bodies continue the cycle anew by infecting new host cells.

All of these pathogens infect epithelial cells specific to the infection location. Rickettsiae and chlamydiae begin in the cell phagosome and both have mechanisms for evading host defense mechanisms. The chlamydiae-host interactions discussed in this paper are elaborate. This paper did not even begin to cover all the details of the events that take place. Further studies of this interaction should lead to more interesting and unexpected events. It is interesting how different organisms and non-organisms (viruses) share unusual traits of the host-parasite interactions. One might think that these traits would be unique to the one organism because of their complexity but as seen here they are not.

References Cited:

(1) Holt et al. Bergey?s Manual of Determinative Bacteriology. Baltimore: Williams and Williams, 1994.

(2) Madigan, Michael et al. Brock Biology of Microorganisms. Upper Saddle River: Prentice Hall. 1997.

(3) Moulder, James W. Rickettsia species (as organisms). 1990. Annual Review Microbiology. 44:131-153.

(4) Winkler, Herbert H. Interaction of Chlamydiae and Host Cells In Vitro. 1991. Microbiological Reviews. 55:143-190.