FREE ESSAY ON THE DISEASE STATE OF CHLAMYDIA

THE DISEASE STATE OF CHLAMYDIA

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.