Treatment of Chlamydia trachomatis Infection

Essential Guide to Cure Chlamydia

Is Chlamydia easily curable? The Answer is a big Yes! Chlamydia is one of the sexually transmitted diseases with proven treatment methods. In fact, there are two main treatment options available both of which have guaranteed results: Conventional medicine and natural medicine. These treatment options And lots of other previously unknown facts about Chlamydia have been explained at great length in this eBook. The Essential guide to Cure Chlamydia unveils the mystery of Chlamydia and methodically presents all the important bits of information that you should know about Chlamydia. The Banish Chlamydia Book tackles the sensitive subject of Chlamydia from the perspective of a professional and presents you with a goldmine of information and facts in a way that has never been done before.

Essential Guide to Cure Chlamydia Summary

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Disruption of the Microtubule Cytoskeleton by Intraphagosomal Pathogens

Upon entry, movement towards the microtubule organizing center (MTOC) in a dynein-dependent way has been observed for several intracellular bacteria such as Chlamydia trachomatis 96, 97 and C. jejuni 95 . Chlamydia phagosomes for example, move towards the minus end of microtubules and aggregate at the MTOC. Trafficking towards MTOC is dynein-dependent although the activating function of the dynactin complex is replaced by still unidentified chlamydial protein(s). Importantly, chlamydial transcription and translation are required for intracellular trafficking 97 .

Phagosome Content in and Accessibility for Lipids

This is a relatively little studied field. The Chlamydia-containing vacuole is the paradigm for labeling live, infected cells with lipid derivatives to probe their accessibility to a pathogen-containing phagosome. This vacuole intersects with the trafficking of certain sphingomyelin- and cholesterol-containing vesicles from the trans-Golgi network to the cell surface. Fluorescent lipid derivatives, such as NBD-C(6)-ceramide, NBD-glucosylceramide or NBD-sphingomyelin were used to probe the accessibility of these lipids to the Chlamydia vacuole 37 . The experiments showed that while the glucosylceramide compound was not retained in the vacuole, sphingomyelin was.

An Ecological View of Intracellular Life

Nutrient limitation - the bacteria's Achilles heel - is targeted by the host response in an interferon g (IFNg)-induced manner. Activated macrophages express the gene for indoleamine 2,3-dioxygenase (IDO), which depletes tryptophan by degradation to kynurein 57 . Sequestration of C. trachomatis from tryptophan drives the bacteria to differentiate into the nongrowing residual body form and causes latent infection. The genome of C. psittaci contains a more complete tryptophan synthesis machinery and resistance to IDO of this Chlamydia species is due to efficient recycling of the amino acid 57 . Genome reduction is a common consequence of colonization for pathogens or symbionts which became highly adapted to the intracellular lifestyle and entirely dependent on their host cells. This is seen in diverse obligate intracellular microbes such as the insect symbionts of the Buchnera genus, or M. leprae, Rickettsia or Chlamydia species, as well as in extracellular Mycoplasma species. The host...

Microbe Containing Vacuoles

The separation of MCVs by ultracentrifugation normally requires two centrifuga-tion steps to achieve sufficient homogeneity. The first step is usually a sucrose gradient and the second a Ficoll or sucrose cushion. Such procedures have been applied to Gram-positive as well as Gram-negative bacteria 35 . Using variations on this common theme, vacuoles containing mycobacteria (M. tuberculosis and M. avium) 10, 36 , Chlamydia psittaci 37 and Francisella tularensis 38 have been purified and used for comparative electrophoretic gel analysis. The mixing of 35 S-Met metabolically labeled macrophages with nonlabeled M. avium-containing macrophages before lysis did not reveal specific selection of contaminating proteins in purified MCVs, with a global contamination level estimated to be a low 6-8 10 .

Intracellular Symbionts Tamed or Acclimatized Parasites

The close relatives of some intracellular symbionts are important bacterial pathogens, which employ the intracellular niche as a survival mechanism, though with the outcome of disease. Legionella-, Francisella-, Chlamydia- and Rickettsia-like species have been found in free-living amoeba. Under experimental conditions, L. pneumophila can infect up to 14 amoeba species, including Hartmanella and Acanthamoeba spp., and two species of ciliated protozoa, whereas its close relative, the rarely pathogenic L. micdadei, only infects Hartmanella amoebae 33, 43 . Compared with L. pneumophila, L. micdadei inhabits a different intra-amoeba compartment and does not exit through pore formation and cytolysis 44 . L. micdadei may therefore represent an earlier stage during the evolution of L. pneumophila to become a successful survivor and ultimately a parasite of amoeba.

Proteomic Analysis of Pathogen Induced Changes to Phagosome Identity

So far, comparative proteomic studies of MCVs have been performed only by 2DE and mainly with mycobacteria-containing vacuoles. Proteomics studies have shown that internalized mycobacteria do not fundamentally change phagosome protein composition. Indeed, comparing endolysosomes to live and dead M. bovis BCG-containing vacuoles isolated by organelle electrophoresis from the mouse macrophage cell line J774, only few marked differences are observed after 1 h of infection 39, 42 , the protein coronin being one of the characteristics of live MCVs. The differences are no larger when comparing 2-h-old M. avium-containing vacuoles isolated on gradients from J774 macrophages with broth-cultured bacteria and LBPs isolated after the same maturation time 10 . Proteomics studies also highlighted that the dissection of pathogen-induced changes in MCV protein patterns is also dependent on the host. The pattern of M. avium-containing vacuoles isolated after 5 days of infection in bone marrow-derived...

Short History of Theories and Discoveries

Clamydia Microscope

The identification of intracellular survival mechanisms was made possible by novel techniques in cell biology and the arrival of modern molecular genetics. J. A. Armstrong and Philip D'Arcy Hart 5, 6 were the first to show inhibition of phagolysosome fusion by the tubercle bacillus. Similar peculiarities of Toxoplasma gondii- and Chlamydia psittaci-containing vacuoles were published in 1979 and 1981, respectively 7, 8 . In the last decade of the twentieth century, many virulence traits of intracellular microbes were elucidated. Genome analyses and molecular techniques, paired with novel model systems such as yeast two-hybrid screening technology, uncovered pathogenicity islands and plasmids, virulence factors, as well as host cell target structures. It was discovered that throughout evolution there must have been a tremendous horizontal gene transfer between different microbes as well as between bacteria and eukaryotes (Chapter 2). Many of those pathogens and their virulence traits...

How to lose the cell wall without dying

One group, the Mycoplasma, comprises mostly parasites, many of which live inside other cells. Mycoplasma cells are tiny, with very small genomes. M. geni-talium, discovered in 1981, has the smallest known genome of any bacterial cell, encoding fewer than 500 genes. Despite its simplicity, it ranks among the most common of sexually transmitted diseases, producing symptoms similar to Chlamydia infection. It is so small (less than a third of a micron in diameter, or an order of magnitude smaller than most bacteria) that it must normally be viewed under the electron microscope and difficulties culturing it meant its significance was not appreciated until the important advances in gene sequencing in the early 1990s. Like Rickettsia, Mycoplasma have lost virtually all the genes required for making nucleotides, amino acids, and so forth. Unlike

Look Through the Microscope of Evolution

Mixotricha Paradoxa Diagram

On several occasions later in evolution, a-proteobacteria such as Wolbachia, Rickettsia and Ehrlichia species, as well as members of the Chlamydiales became settlers of eukaryotic cells as highly specialized obligate intracellular mutualists or pathogens. In free-living amoeba, more than 20 bacterial symbionts have been identified so far, belonging to the a-proteobacteria, b-proteobacteria, Bacteroidetes and Chlamydiales 18-20 . Interestingly, symbiotic Chlamydia species in amoebae have a biphasic lifecycle between metabolically active reticulate and inactive elementary bodies similar to that of pathogenic species in mammals, suggesting common ancestry between the groups. Among amoebae symbionts, differentiation between symbiosis and parasitism is difficult. In the case of Parachlamydia-related symbionts, their association with amoebal partners can also be detrimental to the host cell as they lyse their hosts at temperatures above ambient. In contrast, Neohartmanella hartmanellae is a...

Gene Transfer in Intracellular Bacterial Parasites

Chlamydophila Trachomatis

Trafficking for intracellular bacteria can be categorized into intraphagosomal and intracytoplasmic pathways, in which different relationships with the host cell compartment may involve different modes ofgene transfer and different types ofacquired genes. Intraphagosomal pathogens include Afipia, Brucella, Burkholderia, Chlamydia, Coxiella, Ehrlichia, Francisella, Legionella, Mycobacterium, Rhodococcus, Nocardia and Salmonella, while intracytoplasmic pathogens include Listeria, Rickettsia and Shigella 6, 9, 35 . Specific genes are major targets for gene transfer 6 . These include those encoding proteins for type III and IV secretion systems, which are responsible for infection virulence, and polymorphic surface proteins, which are responsible for attachment and or antigenic variation. As expected, genes involved in housekeeping functions have been documented to undergo gene transfer less frequently 6 . Using sequences from various prokaryotes and eukaryotes in 2001, Koonin et al. 3...

Intraphagosome Ion Concentrations

A pioneering study that fulfilled at least some of these criteria 31 investigated the concentrations of calcium, potassium and sodium ions and pH, respectively, in Chlamydia trachomatis-containing vacuoles. All these concentrations were found to be the same in both cytosol and vacuole. It was concluded, in context with earlier studies, that substances smaller than some 500 Da could cross the vacuole membrane.

Infection of Drosophila Phagocytes

Drosophila melanogaster cells such as primary macrophage-like phagocytes (hemocytes, differentiated plasmatocytes) and phagocytic cell lines can also be used to analyze the host-pathogen interaction. A major advantage of using Drosophila cells is the huge number of mutants that are defective in different aspects of the immune response and the relative ease with which single gene activities can be repressed by inhibitory RNA. The D. melanogaster-derived cell line S2, which was originally isolated from a 24-h-old embryo, has been used to study intracellular pathogens including L. monocytogenes, M. marinum, M. fortuitum, Chlamydia trachomatis and Ehrlichia chaffeensis 59 . S2 cells are classified as phagocytic hemocytes and known to be responsible for the production of antimicrobial peptides. Recent reports using RNA interference in Drosophila S2 cells helped to identify hundreds of host factors that affect L. monocytogenes entry, vacuole escape, intracellular growth and LLO...

Metabolic State

Modifications in respiratory state from aerobic to microaerophilic to anaerobic as murine infection continues 33 . The changing metabolic and respiratory state of intracellular bacteria is best exemplified, however, in bacteria that cycle between vegetative and replicative stages, such as Chlamydia trachomatis and Legionella pneumophila. The chlamydial elementary body (EB), which survives extracellularly and is responsible for cell invasion, differentiates into the reticulate body (RB), which replicates intracellularly, before redifferentiation back into EB for release and reinfection. Shaw et al. 34 followed the gene expression profile of C. trachomatis after epithelial cell infection, and identified sets of genes regulated at early mid and late stages of infection. The early genes encode functions involved in the establishment of the chlamydial inclusion body and the acquisition of nutrients the mid-stage genes for the rapid multiplication of bacteria and late stage genes, the...