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PubMed1982

The relation of basic biology to pathogenic potential in the genus Chlamydia.

Chlamydiae are obligately intracellular procaryotic parasites, and their activities as agents of human disease are determined to a large degree by their intracellular way of life. The inside of a host cell is a hostile environment, and few microorganisms survive and multiply intracellularly. Those that do have evolved adaptations that fit them for life inside other cells. Apart from the viruses, chlamydiae are the infectious agents most highly adapted to intracellular life. Of all the properties of chlamydiae, the ones most likely to determine their pathogenic potential are those that reflect their adaptations to life inside host cells. Wherever possible, these chlamydial activities will be indentified and described.

Adaptation, Physiological↗
PubMed1982

Three novel manifestations of chlamydia trachomatis infection- endometritis, perihepatitis and meningoencephalitis.

The present communication discusses the possibility of endometritis, perihepatitis and meningoencephalitis being three conditions associated with Chlamydia trachomatis infection. Chlamydial infection of the endometrium can occur as one manifestation of an ascending genital infection also affecting the Fallopian tubes. Perihepatitis may be another manifestation in cases of acute chlamydial salpingitis. However, both chlamydia-associated endometritis and chlamydia-associated perihepatitis can occur in the absence of tubal infection. In cases of meningoencephalitis, evidence of infection with TRIC agents (C. trachomatis) have been documented.

Chlamydia Infections↗
PubMed1979

Optical demonstration of Chlamydiae in cell cultures by means of fluorochrome 33,258 H.

Fluorochrome 33,258 H, a bisbenzimidazole, was employed for demonstrating Chlamydiae in cell cultures, and proved to be particularly suitable for illustrating the unique intracellular reproduction processes of these organisms. The staining procedure is simple and permits a selective differentiation of chlamydial inclusions and their developmental processes in the cell. Contrary to other staining methods, all stages of the chlamydial reproduction cycle can be illustrated thus permitting the early demonstration of Chlamydiae in the cell. The procedure is suitable not only in experimental investigations on Chlamydiae but also in clinical diagnostics.

Cell Differentiation↗
PubMed1992

Detection of Chlamydia trachomatis by the polymerase chain reaction in young patients with acute epididymitis.

Specimens from 11 patients presenting with acute epididymitis were tested for the presence of Chlamydia trachomatis by an enzyme immunoassay (EIA), growth in McCoy cells and the polymerase chain reaction (PCR), and for other microorganisms by standard laboratory techniques. Chlamydia trachomatis urethral infection was detected in four patients by tissue culture, in three patients by EIA and in nine patients by PCR. These findings confirm the usually low detection rate of Chlamydia trachomatis by conventional tissue culture and EIA. Detection by PCR indicated both the diagnostic value of this technique and the importance of this organism in epididymitis.

Acute Disease↗
PubMed1993

Acute lower respiratory tract infection associated with Chlamydia pneumoniae in Germany.

Serum specimens from 223 patients with acute lower respiratory tract infection were examined for antibodies to Chlamydia pneumoniae using the microimmunofluorescence test. Antibodies to Chlamydia pneumoniae were detected in 18 (20%) of 91 children and 64 (48%) of 132 adults. Among those individuals, 4 (4%) children and 15 (11%) adults had elevated IgG antibody titres indicating acute or recent infection. Specific IgM antibodies were observed in two patients. These results suggest that a significant proportion of lower respiratory tract infections in Germany is caused by Chlamydia pneumoniae.

Acute Disease↗
PubMed1987

Comparative in vitro activity of A-56268 (TE-031) against gram-positive and gram-negative bacteria and Chlamydia trachomatis.

The in vitro activity of A-56268 (TE-031) was determined and compared with that of 13 antibiotics against 401 gram-positive and gram-negative bacteria and 11 strains of Chlamydia trachomatis. A-56268 was very active against methicillin-susceptible Staphylococcus aureus and Neisseria gonorrhoeae, and was among the most active of the agents tested against Listeria monocytogenes, streptococci and Chlamydia trachomatis. It was moderately active against Haemophilus spp., Vibrio spp., Campylobacter jejuni and Campylobacter fetus subsp. fetus. It was inactive against enterococci, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Campylobacter coli, Salmonella spp., Shigella spp. and Yersinia enterocolitica. A-56268 was not consistently bactericidal or more active than erythromycin for any organism except Chlamydia trachomatis.

Animals↗
PubMed1994

Detection of Chlamydia pneumoniae in clinical specimens by polymerase chain reaction using nested primers.

A nested primers strategy was used to develop a two-step PCR test for the direct species-specific detection of the 16s rRNA gene of Chlamydia pneumoniae. This test was applied to 58 nasopharyngeal or oropharyngeal swab specimens collected from patients in studies of community-acquired pneumonia and in a local outbreak of respiratory disease. Twelve patients (21%) showed evidence of Chlamydia pneumoniae infection in serological tests (7/56; 13%), culture (8/58; 14%) or PCR (10/58; 17%). Nested PCR but not single-step PCR was found to be as sensitive as culture or serology for detection of infection with this organism. In summary, nested PCR can be useful in direct testing of clinical specimens for Chlamydia pneumoniae, making additional DNA purification steps unnecessary.

Amino Acid Sequence↗
PubMed1988

Immune responses of mice after conjunctival exposure to Chlamydia trachomatis serovar A.

CBA/J mice were inoculated in the lower conjunctival sac with live elementary bodies (EBs) of Chlamydia trachomatis serovar A. Recovery of chlamydia after exposure was done by culture of conjunctival swabs and draining lymph node (D-LN) cells in McCoy cells grown on coverslips in isolation vials. Cellular immune responsiveness was measured by lymphocyte proliferation assay of D-LN cells stimulated with irradiated EBs of serovars A, C, or L2. Humoral immunity was measured by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Chlamydia were consistently isolated from the conjunctiva and from the D-LN at 1 and 7 days after exposure respectively. Intermittent isolations were obtained from the conjunctiva up to day 4 and from the D-LN up to day 14 after a single exposure. Serovar A EB-stimulated lymphocyte proliferation was strong by 1 week after conjunctival exposure, but by 4 and 5 weeks, blastogenic responsiveness was very low. This lack of responsiveness may reflect a state of immunosuppression. Responses to serovars C and L2 EBs were consistently lower than to serovar A EBs. Serum IgG antichlamydia antibodies were not detected by ELISA until 2 weeks after exposure, peaked by 4-5 weeks, and decreased between 5 and 7 weeks after exposure. The IgM response was minimal at all times tested. There was, however, a modest increase in IgM antibodies at 3 and 5-7 weeks after exposure. Immunoblot analysis showed reactivity of mouse serum antibodies with polypeptide bands of 30, 41, and 52 kD at 3 and 4 weeks post exposure and predominantly with the 52 kD moiety at 5 weeks post exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Experimental genital tract infection with Chlamydia psittaci (GPIC agent) in male rats.

The course of experimental chlamydial infection of the male genital tract was studied. Inoculation of the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC agent) into the vas deferens of rats resulted in chlamydial infection of the epididymis, testis and the prostate gland. The inflammatory response was most prominent at 14 days after infection. Chlamydiae were recovered from the epididymides and the prostate glands for up to 90 and 60 days post inoculation, respectively. Histopathological changes associated with chlamydial infection of the epididymis or prostate gland were characterized by intratubular and interstitial purulent inflammation. Chlamydia-specific IgM- and IgG-antibodies were found in sera of nearly all infected animals. Results of this study indicate that this animal model may be useful to study the pathogenesis, immune responses and sequelae of chlamydial infections of the male genital tract.

Animals↗
PubMed2002

[Chlamydia pneumoniae and cytomegalovirus in degenerative aortic valve stenoses].

Recent evidence suggests a causal relationship between inflammatory as well as infectious pathomechanisms and valvular degeneration. Based on the concept of chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infections, and of variable stressors working on valvular microecology, the present study sought to assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of CMV, of macrophages and of the human homologue hHSP60. Serial sections of high-grade degenerated native (n = 16) and prosthetic (n = 6) aortic valves were analyzed by immunohistochemistry for the presence of these determinants. Degenerated aortic valves revealed prevalence of Chlamydia pneumoniae in 41% (10 of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64% (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were predominantly found in valvular fibrosa; CMV showed a second predilection site at the ventricular luminal border. Both microorganisms revealed a strong correlation between each other (r = 0.73; p < 0.001) as well as with hHSP60 (cHSP60: r = 0.74; p < 0.001; CMV: r = 0.80; p < 0.001). Macrophage infiltration correlated with cHSP60 (r = 0.78; r < 0.001), CMV (r = 0.78; r < 0.001) and hHSP60 (r = 0.56; r = 0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was increased more than 5-fold in prosthetic valves compared to native valves (p = 0.017, p = 0.002 and p = 0.005). In summary, valvular infections of Chlamydia pneumoniae and of cytomegalovirus are frequently seen in degenerated aortic valves, irrespective of native or prosthetic origin. Colocalization of both HSP60 homologues and cytomegalovirus within macrophages in valvular fibrosa points to regional stressor effects that might be at least partly attributable to chronic persistent pathogen burden and molecular mimicry.

Aged↗
PubMed1998

Viability and gene expression in Chlamydia trachomatis during persistent infection of cultured human monocytes.

The principal host cell for persistently infecting synovial Chlamydia trachomatis is the macrophage. During infection of human monocytes/macrophages in culture this bacterium displays aberrant morphology and produces no new elementary bodies, reflecting the situation in synovium. Here we investigate the metabolic status of C. trachomatis (serovar K) during an extended infection of human peripheral monocytes in vitro. Using reverse transcription-polymerase chain reaction assays, we have shown that primary transcripts from the chlamydial rRNA operons are present throughout a 10-day course of infection. Other assays targeting mRNAs from chlamydial genes encoding r-proteins S5 and L5, the glycyl-tRNA synthetase, the 60-kDa cysteine-rich outer membrane protein, and the KDO transferase indicate that these messengers are also present throughout the entire 10-day period. The gene encoding the 57-kDa heat-shock protein (hsp60) is expressed by the bacterium throughout the 10-day infection of cultured monocytes, but transcript levels from the gene encoding the major outer membrane protein (omp1) appear to be attenuated. Western analyses targeting these latter proteins confirm the presence of the hsp60 gene product, and the virtual absence of major outer membrane protein, in chlamydia-infected cultured human monocytes. Thus, during extended infection of human monocytes in vitro, chlamydia are non-productive but transcriptionally active; the pattern of transcriptional activity reflects that known for persistent C. trachomatis infection in vivo in synovial tissue.

Antibodies, Monoclonal↗
PubMed1999

Expression of interferon regulatory factors and indoleamine 2,3-dioxygenase in Chlamydia trachomatis-infected synovial fibroblasts.

Synovial fibroblasts probably represent host cells for Chlamydia trachomatis during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-beta (IFN-beta) in response to chlamydial infection. IFN-beta expression can be activated by interferon regulatory factor-1 (IRF-1) and interferon-stimulated gene factor 3gamma (ISGF3gamma). In this study, we demonstrate that infection of synovial fibroblasts with C. trachomatis serotype D induced the expression of IRF-1 mRNA as shown by reverse transcription-PCR. Tumor necrosis factor-alpha (TNF-alpha) stimulation enhanced IRF-1 mRNA levels in infected cells and was required to detect IRF-1 protein by immunoblotting. The level of constitutively expressed IRF-2 was not significantly affected after infection. C. trachomatis was found to cause an up-regulation of ISGF3gamma protein in synovial cells. Induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellular infection by chlamydiae. It has been described that IRF-1 can induce IDO gene expression. Infection of synovial fibroblasts alone in the absence of exogenous cytokine induced the expression of IDO mRNA which was enhanced by TNF-alpha treatment. The stimulation of IRF-1, ISGF3gamma, and IDO expression was most effective when viable chlamydiae were used as inoculum. Neutralization of IFN-beta in the culture medium of infected cells diminished but did not abrogate expression of IRF-1, ISGF3gamma, and IDO. The increased production of IRF-1 and ISGF3gamma in C. trachomatis-infected synovial fibroblasts may contribute to induction of IFN-beta and IDO.

Antibodies↗
PubMed2002

Chlamydia pneumoniae DNA in peripheral venous blood samples from patients with carotid artery stenosis.

In the study presented here, peripheral blood specimens obtained from patients with atherosclerosis were examined for the presence of Chlamydia pneumoniae to determine whether these specimens can be used for routine testing. Chlamydia pneumoniae DNA was detected in 7 of 56 patients with carotid stenosis and in three of four patients with other atherosclerotic diseases, but it was not detected in any of 50 healthy controls or in any of 59 age- and gender-matched patients suffering from other nonatherosclerotic diseases. IgG antibodies indicative of an active Chlamydia pneumoniae infection were detected by microimmunofluorescence in two of nine PCR-positive patients but in none of 41 PCR-negative patients. Four of nine serum samples obtained from PCR-positive patients contained IgA antibodies compared to 5 of 41 samples obtained from PCR-negative patients.

Adult↗
PubMed2003

Failure to detect Chlamydia pneumoniae by cell culture and polymerase chain reaction in major arteries of 93 patients with atherosclerosis.

To detect Chlamydia pneumoniae in punch specimens of the aortic wall of 61 patients undergoing coronary-aortic bypass graft, and carotid atheromas of 32 patients undergoing carotid endarterectomy, cell culture (HEp-2 cells) and two polymerase chain reaction assays in two different laboratories were used. All cultures and polymerase chain reaction tests for Chlamydia pneumoniae were negative. Further studies are required to explore the complex relationship between Chlamydia pneumoniae and atherosclerosis.

Aged↗
PubMed2000

Isolation and continuous growth of Chlamydia pneumoniae from arterectomy specimens.

For the purpose of collecting Chlamydia pneumoniae strains of vascular origin that could be grown continuously in vitro, a cell culture system has been established. Using different types of vascular specimens obtained from 38 patients, Chlamydia pneumoniae could be isolated in three (7.9%) cases. The strains were obtained from specimens of the carotid artery, the femoral artery and an infrarenal aneurysm of the abdominal aorta of three male atherosclerosis patients. Thus, viable Chlamydia pneumoniae strains are also present in vascular regions other than those hitherto described.

Aged↗
PubMed2004

A prediction model for community-acquired Chlamydia pneumoniae pneumonia in hospitalized patients.

BACKGROUND: The objective of the study was to identify factors that help to predict community-acquired Chlamydia pneumoniae pneumonia in hospitalized patients. PATIENTS AND METHODS: Clinical data of 83 patients with serologically confirmed C. pneumoniae pneumonia were compared with the data obtained from 72 patients with bacterial pneumonia. The criteria of bacterial pneumonia included positive blood and/or sputum cultures and negative serology for Mycoplasma pneumoniae, Chlamydia psittaci, Chlamydia pneumoniae and Coxiella burnetii. The data collected included demographics, chronic diseases, pre- and post-hospitalization course of pneumonia, clinical data on admission and laboratory findings. Descriptive statistical analysis, involving numerous variables, was followed by univariate and multivariate logistic regression analysis. RESULTS: Two different situations, one including demographic data and information on the pre-hospitalization course of pneumonia, and another based on clinical information on admission and on laboratory results, were modeled using multivariate logistic regression. Several variables selected from these two models were incorporated into the third model, and the following four variables were found to have the highest predictive value of C. pneumoniae pneumonia: nursing home residence (odds ratio [OD] 3.73, 95% confidence interval [CI] 1.39-10.06), low c-reactive protein (CRP) levels (OD 5.99, 95% CI 1.82-19.67), nonproductive cough (OD 0.32, 95% CI 0.14-0.73), and a normal urinalysis (OD 0.38, 95% CI 0.17-0.83). CONCLUSION: Our findings seem to allow for a more reliable differentiation between C. pneumoniae pneumonia and other bacterial pneumonias, but further investigations will be needed to validate the proposed model.

Adolescent↗
PubMed1994

The core group revisited: the effect of partner mixing and migration on the spread of gonorrhea, Chlamydia, and HIV.

A set of differential equations are used to model the spread of sexually transmitted diseases (STDs) in a one-sex population that includes a core group of highly sexually active subjects. The effects of partner mixing between groups and migration to and from the core on the equilibrium number of infected are shown for gonorrhea, chlamydia, and HIV. The STDs are described by the transmission probability per sexual contact and the duration of infectiousness. Partner change and intercourse frequencies are estimated from sexual survey data on heterosexual behavior. The core group is small (3% of the total population) with a partner change frequency 15 times and an intercourse frequency 2 times that of the remaining population. The degree of partner mixing and migration between the two groups can be varied. The number of sexual contacts in the three types of partnerships (core-core, "mixed," remaining population-remaining population) is also modeled. The mixed partnerships are assumed to be casual and to have a low frequency of intercourse. The model is fairly simple, and the emphasis is on qualitative rather that predictive results. The effects of partner mixing are found to be strikingly different for gonorrhea, chlamydia, and HIV. With increasing partner mixing between groups, gonorrhea shows a small increase and then a decrease in the total number of infected, whereas chlamydial infection shows a strong increase. For HIV infection the effect depends on the transmission probability; when it is 0.001 per sexual contact, the number of infected with HIV is almost unaffected by the partner mixing, and when the transmission probability is 0.002 per sexual contact, there is a strong increase in the number of HIV infected with increasing partner mixing. The effects of migration are also different for each disease. With increasing migration between groups, gonorrhea is almost unaffected in the total number of infected, whereas chlamydial infection shows a strong increase. For HIV the effect again depends on the transmission probability; when it is 0.001 per sexual contact, the number of infected with HIV shows a strong decrease, and when the transmission probability is 0.002 per sexual contact the number of HIV infected reaches its maximum for medium strong migration. A sensitivity analysis shows that for all three diseases the basic reproductive ratios (R0) and the total number of infected are sensitive to duration of infectiousness. In addition, for gonorrhea and chlamydia, RO is sensitive to the partner change rates in the core, whereas for HIV, RO is sensitive to the frequency of intercourse in the core.(ABSTRACT TRUNCATED AT 400 WORDS)

Chlamydia Infections↗
PubMed1986

Chlamydia trachomatis (L2 serovar) binds to distinct subpopulations of human peripheral blood leukocytes.

We have previously shown that infants with pneumonitis caused by Chlamydia trachomatis, an obligate intracellular bacterium, possess increased percentages of B lymphocytes but not T lymphocytes in their peripheral blood. It was then demonstrated that chlamydiae induce proliferation in vitro of human peripheral blood B lymphocytes and, in the presence of T cells, differentiation of B cells to immunoglobulin-secreting cells. In this study, we show that C. trachomatis (L2 serovar) binds preferentially to 50% of human B lymphocytes from peripheral blood but only to a small percentage, if any, of T cells. Both monocytes and granulocytes bind and ingest chlamydiae. Despite chlamydial binding to B cells and ingestion by monocytes, no uptake by B cells and limited growth (fewer than 0.5% inclusion-containing cells) in monocytes occur. There is a dramatic decrease in the percentage of cells associated with the bacteria after culture. These results are the first demonstration of binding of C. trachomatis (L2 serovar) to lymphocytes and represent a direct step toward correlating physical interactions between bacteria and lymphocytes with specific immunostimulatory activities in vitro.

Adhesiveness↗