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PubMed2001

Substrate-specific diffusion of select dicarboxylates through Chlamydia trachomatis PorB.

Chlamydiae contain two porins, MOMP and PorB, that facilitate diffusion of solutes through the outer membrane. MOMP is a general porin that permits the diffusion of a wide variety of compounds including carbohydrates and amino acids. The relative inefficiency of PorB as a general porin and its low abundance in the outer membrane suggest that it may function as a substrate-specific porin. The tricarboxylic acid (TCA) cycle of chlamydiae is incomplete and to function would require the exogenous acquisition of 2-oxoglutarate or glutamate. A liposome-swelling assay for anions as well as an enzyme-linked liposome assay were used to demonstrate the efficient diffusion of dicarboxylates such as 2-oxoglutarate through PorB. These data demonstrate that PorB is a dicarboxylate-specific porin that may feed the chlamydial TCA cycle and provide chlamydiae with carbon and energy production intermediates.

Bacterial Outer Membrane Proteins↗

PubMedDate not supplied

[Etiology of lower acute respiratory infections in hospitalized infants. 3. Investigation of Chlamydia trachomatis].

Five infants with Chlamydia trachomatis associated pneumonia are analyzed. They were diagnosed out of 80 infants admitted to the hospital with pneumonia whose etiology was studied for virus, bacteria and Chlamydia trachomatis. Serum IgM antibodies to Chlamydia tr. were measured by indirect immunofluorescence (IIF), which is considered to be specific in high titers (1 greater than or equal to 32). The five cases represented 10.4% of infants studied younger than six months. One child was born by cesarean section suggesting the possibility of other non oculogenital still undefined mechanism of transmission. Clinical symptoms and laboratory findings were characteristics of those described in Chlamydia tr. pneumonia. Chlamydia trachomatis must be considered an etiologic agent in infantile pneumonia specially in the first six months of life. The high specificity and sensitivity of the IFF makes this serologic test the best non-invasive method for diagnosis of Chlamydia tr. pneumonia currently available.

Antigens, Bacterial↗

PubMed1998

Secretion of cytokines by human synoviocytes during in vitro infection with Chlamydia trachomatis.

OBJECTIVE: Since Chlamydia-induced reactive arthritis is associated with the presence of viable chlamydiae in the synovial membrane, we studied the ability of Chlamydia trachomatis to stimulate a cytokine response by fibroblast-like synoviocytes in culture. METHODS: Fibroblast-like cells derived from biopsies of the synovial membrane were infected with Chlamydia trachomatis serotype E. Interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) were determined using bio-assays. Granulocyte macrophage colony stimulating factor (GMCSF) was quantified by ELISA. RESULTS: Fibroblast-like synovial cells were capable of supporting chlamydial growth in vitro. Chlamydia trachomatis stimulated synoviocytes to produce IL-6, TGF-beta, and GMCSF. IL-1beta increased the production of IL-6 and GMCSF by mock-infected and infected cells. Treatment of synoviocytes with interferon-gamma resulted in the release of TNF-alpha in response to chlamydial infection. CONCLUSION: Chlamydia-induced cytokine release from synovial fibroblasts may contribute to alterations in the synovial membrane promoting the development of joint inflammation.

Bacteria↗

PubMed1994

[In situ hybridization of cells infected by Chlamydia trachomatis].

Hybridization in situ of chlamydia trachomatis allows identification of the bacteria. Moreover exact chlamydia trachomatis localization at tissue level can be demonstrated. It seems to us very important to know for instance in conjunctiva were chlamydia trachomatis are located. We used DNA DIGOXIGENIN labelled plasmidic probe of 503 b.p. Detection of chlamydia trachomatis on paraffin embedded cells becomes possible. Specificity is 100% as plasmidic sequence is not found in other bacteria. Sensitivity seems to be good quality on experimental model. At present time, it is under clinical evaluation. This method could complete PCR for chlamydia detection in case of controversial diagnosis.

Chlamydia Infections↗

PubMed2002

Chlamydia trachomatis - the agent.

Chlamydiae are obligate intracellular bacteria, parasitizing eukaryotic cells. Chlamydia trachomatis, C. psittaci and C. pneumoniae are the three species of chlamydiae pathogenic to humans. C. trachomatis shows a tropism for the genital and conjunctival epithelia and consists of 19 different serovars which are pathogenic predominantly for the urogenital tract.A distinguishing feature of chlamydiae is their transition between the infectious elementary body that enters the host cell and the non-infectious reticulate body that replicates intracellularly within an inclusion that does not fuse with lysosomes. Chlamydiae depend for some functions upon the host cell; in particular, chlamydiae have little capacity for generating energy. The complete sequence of the 1000-kb chromosome of C. trachomatis is known, as are most of the genes located on the 7.5-kb cryptic plasmid. Recently, several concepts about the biology and the metabolic pathways of C. trachomatis have been revised in relation to the genome sequence, and different novel proteins have been described.

Chlamydia Infections↗

PubMed1993

Chlamydia trachomatis genital infections.

Chlamydia trachomatis genital infections are among the most common sexually transmitted diseases in the United States today. Although these organisms are obligate intracellular pathogens, they more closely resemble bacteria than viruses. C. trachomatis is responsible for considerable morbidity in women, causing urethritis, cervicitis, endometritis, and pelvic inflammatory disease. The latter complication is associated with a high incidence of infertility and ectopic pregnancy, even when the infection is asymptomatic. In young men, C. trachomatis is a common cause of urethritis and epididymitis. Diagnostic tests include tissue culture which has the greatest sensitivity and specificity but is difficult and costly, and various antigen assays which are useful in high-risk, high-prevalence populations. Treatment is effective with doxycycline or erythromycin, but success also depends on appropriate follow-up and empiric treatment of sexual partners. Control of C. trachomatis genital infections is crucial to the control of all sexually transmitted diseases including HIV infection.

Chlamydia Infections↗

PubMed1981

Polypeptide composition of Chlamydia trachomatis.

Strains of Chlamydia trachomatis representative of 14 serotypes were grown in HeLa 229 cells. HeLa cell susceptibility to chlamydial infection was increased by treating the host cells with DEAE-dextran. Optimal conditions of DEAE-dextran treatment were determined for each serotype of C. trachomatis to maximize chlamydial yields. Chlamydial polypeptides were selectively radiolabelled with 3H-labelled amino acids in the presence of emetine, an inhibitor of HeLa cell protein synthesis. The radiolabelled chlamydiae were purified from host cell components by density gradient centrifugation and their polypeptide composition was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The distribution of the major chlamydial polypeptide of 38 000 to 42 000 daltons amongst the different serotypes correlated closely with the predominant human infections caused by each serotype. Lymphogranuloma venereum agents possessed a unique polypeptide of 118 000 daltons not found amongst trachoma inclusion conjunctivitis strains of chlamydiae. Chlamydial surface polypeptides were selectively radiolabelled with 125I by lactoperoxidase-catalysed oxidation. The major chlamydial polypeptide and polypeptides of 155 000 and 29 000 daltons were thus identified as surface polypeptides of the chlamydial elementary body. It is suggested that the 155 000 dalton polypeptide is a species-specific antigen, the major polypeptide is the principal outer membrane protein, and the 29 000 dalton polypeptide is the type-specific antigen.

Chlamydia trachomatis↗

PubMed2006

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse.

Chlamydia trachomatis is a bacterial pathogen that is a major cause of blindness and infertility in diverse populations across the world. In an effort to model genetic complexities that are observed in human populations and to identify novel genes involved in susceptibility to C. trachomatis, we have adapted a murine model of systemic infection for use in genetic analysis. In this model, chlamydial colonization and replication is measured in the spleens of mice shortly after intravenous delivery of C. trachomatis L2. Here, we show that C57BL/6J and C3H/HeJ inbred mice are differentially susceptible to this systemic infection. Additionally, fibroblasts cultured from C57BL/6J and C3H/HeJ embryos are differentially permissive for chlamydial replication. We have taken advantage of this natural variation to map quantitative trait loci on Chromosomes 2, 3, and 11 that segregate with the bacterial load in F2 cross progeny during the acute phase of C. trachomatis infection in vivo. To validate our mapping results, we also generated mice that are congenic for a portion of Chromosome 11 from the susceptible parent. This congenic interval confers increased susceptibility to C. trachomatis, both in vivo and in vitro, suggesting that our screen identified at least one gene that is involved in cellular resistance to C. trachomatis replication.

Animals↗

PubMed1985

Failure of in vitro fertilization and embryo replacement following infection with Chlamydia trachomatis.

Antibodies to Chlamydia trachomatis were detected in 54 (47.4%) of 114 infertile women attending Bourn Hall Clinic. Antibodies were solely of the IgG class and mainly of a low titer, suggesting past infection. Antibodies were found in significantly more patients with tubal damage (54.4%) than in women whose infertility was due to other causes (16.6%). Seventy-two women completed in vitro fertilization, with 52 having three embryos replaced. We found that this treatment offered the optimum chance of a pregnancy being established, and 20 (38.5%) of these women became pregnant. Antibodies to C. trachomatis were present in only six (30.0%) of the women becoming pregnant, whereas antibodies were found in 21 (65.6%) of those who failed to become pregnant. Thus past infection with C. trachomatis halved the success rate of in vitro fertilization in these patients. The implications of these findings are relevant to all aspects of infertility from prevention to in vitro fertilization treatment.

Adult↗

PubMedDate not supplied

Treatment of Chlamydia trachomatis genital infection.

Chlamydia trachomatis infections are the most frequent bacterial sexually transmitted diseases in the United States, with an estimated 4 million cases occurring annually. The mainstay of treatment for chlamydial infections has been the tetracyclines. Doxycycline, comparable in cost to tetracycline and with a less frequent dosage schedule, is the drug of first choice. Erythromycins are the drugs of choice for infections in pregnant women, nursing mothers, infants, children, and adults unable to tolerate tetracyclines. beta-Lactam antibiotics have had variable efficacy against C. trachomatis infections, although recent studies suggest that amoxicillin may be an effective alternative for C. trachomatis infection during pregnancy. Quinolones are currently being tested and may be used in alternative regimens in the future. The effectiveness of current antimicrobial regimens in preventing long-term complications of chlamydial infections should be determined in research studies.

4-Quinolones↗

PubMed2006

The effect of penicillin on Chlamydia trachomatis DNA replication.

Chlamydia trachomatis L2 was used to infect BGMK cells at an m.o.i. of 1.0, and the developmental cycle was followed by transmission electron microscopy and quantitative PCR (QPCR) for both chromosomal and plasmid DNA. Samples were taken at sequential 6 h time points. Subsequent analysis by QPCR showed that there was an initial slow replication period (0-18 h), followed by a rapid phase (18-36 h) coinciding with exponential division when the DNA doubling time was 4.6 h. Chromosomal DNA was amplified 100-200-fold corresponding to 7-8 generations for the complete developmental cycle. Penicillin (10 and 100 units ml(-1)) was added to cultures at 20 h post-infection (p.i.). This blocked binary fission and also prevented reticulate body (RB) to elementary body transition. However, exposure to penicillin did not prevent chromosomal or plasmid DNA replication. After a short lag period, following the addition of penicillin, chlamydial chromosomal DNA replication resumed at the same rate as in control C. trachomatis-infected cells. C. trachomatis-infected host cells exposed to penicillin did not lyse, but instead harboured large, aberrant RBs in massive inclusions that completely filled the cell cytoplasm. In these RBs, the DNA continued to replicate well beyond the end of the normal developmental cycle. At 60 h p.i. each aberrant RB contained a minimum of 16 chromosomal copies.

Animals↗

PubMed1997

Susceptibility of Chlamydia trachomatis to trovafloxacin.

Chlamydia trachomatis infections are a major cause of morbidity in the sexually active. While current therapy is usually effective, isolates demonstrating relative resistance to erythromycin or heterotypic resistance to erythromycin, tetracycline and their congeners have been described, establishing a need to continue to evaluate other antimicrobial agents for possible efficacy. In this study trovafloxacin, a compound related to the fluoroquinolones, was tested in tissue culture for in-vitro efficacy against 19 strains of C. trachomatis, including three strains known to exhibit heterotypic resistance. All strains were fully sensitive to trovafloxacin with a minimum inhibitory concentration at which 90% of inclusions were reduced (IR90) of 0.05 +/- 0.07 mg/L (mean +/- S.D.). The IR90 for the comparison antibiotics erythromycin, doxycycline and ofloxacin were 0.17 +/- 0.07, 0.10 +/- 0.03 and 0.35 +/- 0.15 mg/L respectively. Trovafloxacin is very active on a weight basis and deserves further evaluation.

Anti-Infective Agents↗

PubMed1991

Simplified microtiter cell culture method for rapid immunotyping of Chlamydia trachomatis.

Serotyping of Chlamydia trachomatis strains usually requires three to six serial passages in shell vials to attain sufficient antigen for typing procedures. To circumvent this problem, we developed a rapid low-passage method for serotyping of C. trachomatis clinical isolates. Isolates with an inclusion count of greater than or equal to 500 per well in primary isolation were inoculated directly onto cell culture monolayers in microtiter plates for typing. Primary isolates with a lower initial inclusion count were passed one to two times in shell vials until there were greater than or equal to 20 inclusions per well and were then inoculated onto plates for typing. Inclusions were grown to maturity and reacted with a panel of 17 C. trachomatis-specific monoclonal antibodies in pools. Wells were then reacted with a fluorescein isothiocyanate conjugate and read by FA microscopy, and the reaction patterns were compared with prototype strain reaction patterns to determine the serotype. By the microtiter method, we successfully typed 1,711 consecutive C. trachomatis isolates; 1,215 isolates (71%) were typed with no or with one passage. The first 209 isolates typed by the microtiter method were also typed by the dot-enzyme-linked immunosorbent assay serotyping method; 100% agreement was demonstrated among strains that were typeable by both methods. We conclude that the microtiter method is extremely useful for accurate serotyping of large numbers of isolates and requires greatly reduced technician time.

Antibodies, Monoclonal↗

PubMed1993

Lack of evidence of a relationship between genital symptoms, cervicitis and salpingitis and different serovars of Chlamydia trachomatis.

Isolates of Chlamydia trachomatis from 424 women were serotyped, and signs and symptoms related to the infecting serovar. Symptoms suggesting genital chlamydial infection were present in 37% of the women, while 15% had clinical findings consistent with lower genital tract infection or ascending infection. Cervicitis, adnexal tenderness and salpingitis were not associated with any specific serovar. On the contrary, the various clinical manifestations tended to occur at similar rates with the different serovars, suggesting a similar pathogenic potential of the serovars detected.

Adult↗

PubMed1995

Chlamydia trachomatis infection update.

Chlamydia trachomatis has become the most common sexually transmitted infection in the United States. Aggressive screening of sexually active young adults is needed, as well as prompt and reliable treatment of infected partners, to mitigate the effects of this disease. Tests using enzyme immunoassay and DNA probe have increased the efficiency of diagnosis through rapid detection, although culture remains the most reliable test. Treatment with single-dose azithromycin is a successful alternative to the definitive treatment, seven days of doxycycline therapy.

Chlamydia Infections↗

PubMed1991

[Urogenital Chlamydia trachomatis infections].

Urogenital Chlamydia trachomatis infections are the most common sexually transmitted diseases which have shown a significant increase in the last few years. This organism presents a major health problem in many countries. It is recognized as the cause of both complicated and uncomplicated infections in men, women and infants passing through an infected birth canal. Tissue culture is accepted as the gold standard in the diagnosis of chlamydial infections. But, since this technique is expensive and cumbersome, antigen detection tests such as DFA and EIA are more widely used. Tetracyclines and erythromycins are the first-choice antimicrobials in the treatment of chlamydial infections.

Chlamydia Infections↗

PubMed2006

A review on infection with Chlamydia trachomatis.

Infection with Chlamydia trachomatis accounts for the most common bacterial sexually transmitted infection in the UK. Men between 20 and 24 years and women between 16 and 19 years have the highest prevalence of chlamydial infection. Because the majority of women with chlamydial infection are asymptomatic, a proportion remains untreated and eventually develops pelvic inflammatory disease (PID). PID can result in ectopic pregnancy, infertility and chronic pelvic pain. Screening for chlamydial infection might reduce the incidence of complications of PID. The advent of nucleic acid amplification tests and single-dose therapy for chlamydial infection has made home testing and easy treatment possible.

Adolescent↗

PubMed1999

A phase-II study of trovafloxacin for the treatment of Chlamydia trachomatis infections.

BACKGROUND: Chlamydia trachomatis can cause an insidious, asymptomatic infection in both men and women. Trovafloxacin, a fluoronaphthyridone antibiotic related to the fluoroquinolones, has broad antibacterial activity that encompasses C. trachomatis. GOAL OF STUDY: We designed a phase-II study to determine the efficacy and safety of trovafloxacin for chlamydial infections. STUDY DESIGN: Four once-daily dosing regimens were used: 200 mg for 7 days, 200 mg for 5 days, 100 mg for 7 days, and 50 mg for 7 days. RESULTS: Sixty-four men and 66 women were enrolled. Of the 73 bacteriologically evaluable patients, 20 received 200 mg for 7 days, 18 received 200 mg for 5 days, 14 received 100 mg for 7 days, and 21 received 50 mg for 7 days. Bacteriologic failure occurred in 1 patient (5%) in the 200-mg 7-day group, 2 patients (14%) in the 100-mg group, and 1 patient (5%) in the 50-mg group. No clinical failures were noted among the 30 C. trachomatis infected men with nongonococcal urethritis, although 1 patient had only improved at the final visit. Safety data were available from 119 patients. Of 86 patients receiving the three highest dosing regimens, 17 (20%) had at least one adverse event, judged treatment-related in only 9 (10 %). Of 33 patients receiving the lowest dose, 5 (15%) had an adverse event, three (9%) of which were considered treatment related. No adverse event was severe. CONCLUSION: In doses ranging from 200 mg to 50 mg daily for a week and 200 mg daily for 5 days, trovafloxacin appears to be effective for chlamydial infections and is well tolerated.

Adult↗