Chlamydia trachomatis

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A Microbial Biorealm page on the genus Chlamydia trachomatis


Contents

Classification

Higher order taxa

Bacteria; Chlamydiae/Verrucomicrobia group; Chlamydiae; Chlamydiae (class); Chlamydiales; Chlamydiaceae; Chlamydia

Genus

Chlamydia

Description and significance

C. trachomatis is an obligate, aerobic, intracellular parasite of eukaryotic cells. It is a Gram-negative bacteria and has a coccoid or rod shape. It has a cytoplasmic membrane and outer membrane similar to Gram-negative bacteria (thus, it being classified as Gram-negative) but, it lacks a peptidoglycan cell wall. C. trachomatis require growing cells in order to remain viable since it cannot synthesize its own ATP. Without a host organism, C. trachomatis cannot survive on its own [3].

C. trachomatis is the leading cause of sexually transmitted disease worldwide--in the United States, alone, over 4 million cases are diagnosed each year. It is also the leading cause of preventable blindness (caused by a chlamydia infection called trachoma) in the world [5]. C. trachomatis is also one of the major causes of pelvic inflammatory disease (PID) and infertility in women [3].

It is important to understand and sequence the genome of C. trachomatis because it would help us better understand its functions as a pathogen--the properties that allow it to live within its human host and its virulence and biological capabilities as a pathogen. Thus, an effort has been made to sequence most of the C. trachomatis genome [2].

Genome structure

Chlamydia trachomatis has a genome that consists of 1,042,519 nucleotide base pairs and has approximately 894 likely protein coding sequences. [2] C. trachomatis strains have an extrachromosomal plasmid, which was sequenced to be a 7493-base pair plasmid. Because there is less than 1% nucleotide sequence variation, ll plasmids from human C. trachomatis isolates are considered to be very similar. All the isolates "are about 7,500 nucleotides long and has eight open reading frames computer-predicted to code for proteins of more than 100 amino acids, with short non-coding sequences between some of them." [1]

Interestingly, in their nucleotide sequence, chlamydial plasmids are more closely related than is the corresponding chromosomal DNA. The plasmid of C. trachomatis is a favored target for DNA-based diagnosis of C. trachomatis because there are approximately 7-10 copies of the plasmid present per chlamydial particle. Its sequence is highly conserved among different isolates of C. trachomatis. Some C. trachomatis strains lack these plasmids, and the consequences aid in detection of the C. trachomatis strain. Plaque purified C. trachomatis that do not contain the plasmids have unusual inclusion morphology, have no glycogen, and show no alteration in antibiotic sensitivity . However, the fact that such strains exist shows that the plasmid is not essential for C. trachomatis survival [1].

Cell structure and metabolism

The life cycle of Chlamydia trachomatis consists of two stages: elementary body and reticulate body. The elementary body is the dispersal form, which is analogous to a spore. The dispersal form is about 0.3 um in diameter and induces its own endocytosis upon exposure to target cells. It is this form that prevents phagolysosomal fusion, which then allows for intracellular survival of the bacteria. Once inside the endosome, the elementary body germinates into the reticulate body as a result of the glycogen that is produced. The reticulate body divides through binary fission at approximately 2-3 hours per generation. The cell body has an incubation period of 7-21 days in the host. It contains no cell wall and is detected as an inclusion in the cell. After division, the reticulate body transforms back to the elementary form and is released by the cell by exocytosis. One phagolysosome usually produces 100-1000 elementary bodies [2].

For metabolism, Chlamydia trachomatis has a glycolytic pathway and a linked tricarboxylic acid cycle. Glycogen synthesis and use of glucose derivatives plays a supporting role in chlamydial metabolism. The presence of metabloic precursors and products, such as pyruvate, succinate, glycerol-3-phosphate and NADH dehydrogenases, NADH-ubiquinone oxidoreductase and cytochrome oxidase indicate that Chlamydia trachomatis uses a form of electron transport in order to produce energy [2].

Ecology

Chlamydia trachomatis is a pathogenic bacteria. It cannot survive outside of a eukaryotic host. In fact, humans are the only known natural host for C. trachomatis. The bacterium is transmitted by sexual contact with an infected individual.[3]

Usually, C. trachomatis is asymptomatic in its hosts, but can cause discharge from the penis, pain and burning during urination,infection or inflammation in the ducts of testicles, and tenderness or pain in the testicles. [3]

Pathology

Chlamydiae replicate intracellularly in what is called an inclusion--a membrane bound structure. This inclusion is able to avoid lysosomal fusion and degradation. Thus, the metabolically inactive elementary body form of chlamydia is able to become the reticulate body. The multiplying reticulate bodies then become elementary bodies again and burst out of the host cell to continue the infection cycle. Since Chlamydiae are obligate intracellular parasites, they cannot be cultured outside of host cells, leading to many difficulties in research [3]. (Also, see Cell Structure Section)

Chlamydia is transmitted through infected secretions only. It infects mainly mucosal membranes, such as the cervix, rectum, urethra, throat, and conjunctiva. It is primarily spread via sexual contact and manifests as the sexually transmitted disease. The bacterium is not easily spread among women, so the STD is mainly transmitted by heterosexual or male homosexual contact [3]. However, infected secretions from the genitals to the hands and eventually to the eyes can cause trachoma [5].

Application to Biotechnology

Using the major outer membrane protein (MOMP) of Chlamydia trachomatis, antibody-based diagnostics as well as recombinant vaccines are being developed. DNA priming followed by protein boosting of MOMP of C. trachomatis has been shown to be promising in developing a vaccine for C. trachomatis. [9] (Also, see Current Research section)

Current Research

The first current research analyzes cytokine and chemokine receptors in C. trachomatis in order to better understand the molecular aspects of C. trachomatis involvement during host response. Blood samples were collected from three healthy donors. Once peripheral blood mononuclear cells (PBMC) were separated from the samples, each sample was infected with elementary bodies of C. trachomatis. Three time points of infection were taken: four hours (active infection), one day (transition), and seven days (persistent infection). After using a microassay and a real time PT-PCR, there was indication of gene expression of genes encoding for inflammatory responses. Conclusively, the study shows that there are several differences between active and persistent chlamydial infections. This study provides a better understanding of the mRNA encoding cytokines, chemokines, and their receptors in C. trachomatis infected host cells [6].

The second current research examines the question of whether or not leukocytes on liquid based cervical cytology can help in predicting C. trachomatisinfections. Samples of cervical smears were taken from a control group of women and a group of women infected with C. trachomatis. Upon examination of these smears, the smears from Chlamydia-infected women had about 30.7 leukocytes, while the smears from the control group had about 11.5 leukocytes. By assessing the leukocytes, researchers were able to see a correlation between the inflammation on liquid based cervical cytology and C. trachomatis infection. [7]

The third current research uses a live-attenuated form of the influenza A virus to provide viral vector for a vaccine against C. trachomatis. This vaccine is tested to be used intra-nasally. In the experiment, mice were intra-nasally immunized with influenza A viral recombinants. The result was a very strong immune, T helper 1, response against intact Chlamydia trachomatis elementary bodies. The genital secretions in the mice showed high levels of specific Th1 cells and elevated immunoglobulin G2a, which indicates a possibility of long term, protective immunity. This study, using C. trachomatis, is very important because it indicates that live attenuated vaccines of the influenza virus could be a new and reliable approach to preventing the spread of sexually transmitted disease. [8]

References

[1]Kalman, Sue et al. 1999. "Comparative genomes of Chlamydia pnuemoniae and C.trachomatis." Nature, 21: 385-389.

[2]Stephens, Richard S. et al. "Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis." Science, 282: 754-759.

[3]Byrne, Gerald I. 2003. "Chlamydia uncloaked." PNSA 100:14. 2003

[4]Mohit Singla & Bikram Bal: "Infectivity Assays For Chlamydia trachomatis". The Internet Journal of Microbiology. 2006; Volume 2, Number 2.

[5]Wang, Y. 1999. "Etiology of trachoma: a great success in isolating and cultivating Chlamydia trachomatis." Chinese Medical Journal 112, 938 - 941.

[6] Hess, S. et al. 2007. "Expression of Inflammatory Host Genes in Chlamydia trachomatis Infected Human Monocytes." Arthritis Research & Therapy. 24;9(3):R54.

[7] Donnellan NM, et al. 2007. "Inflammation on liquid-based cervical cytology: can leukocytes be used to triage for Chlamydia trachomatis testing?" American Journal of Obstetric Gynecology. 196(5):e33-5.

[8]Ananaba GA, et al. 2007. "Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines." Immunology (epub ahead of print).

[9] Brunham, Robert, et al. 2000. "Priming with Chlamydia trachomatis Major Outer Membrane Protein (MOMP) DNA followed by MOMP ISCOM Boosting Enhances Protection and Is Associated with Increased Immunoglobulin A and Th1 Cellular Immune Responses." Infection and Immunity. 3074-3078.

Edited by Christina Bach, student of Rachel Larsen and Kit Pogliano

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