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The major outer sheath protein of Treponema denticola inhibits the binding step of collagen phagocytosis in fibroblasts.

Bacterial infections contribfute to the chronicity of connective tissue lesions in part by perturbing extracellular matrix remodelling processes. We examined a novel mechanism by which the major outer sheath protein (Msp) of the spirochaete Treponema denticola disrupts matrix remodelling mediated by intracellular digestion of collagen. The initial collagen-binding step of phagocytosis was examined in human gingival fibroblasts and Rat-2 fibroblasts. Cells were pretreated with Msp or vehicle, and binding of collagen-coated beads was measured by flow cytometry. Exposure to Msp induced a dose- and time-dependent decrease in cells that bound collagen beads; the inhibition of binding was reversed by absorption with anti-Msp antibodies. Msp-treated fibroblasts remained viable but underwent actin reorganization, including the assembly of a dense meshwork of subcortical actin filaments. Shear force assays showed that Msp abrogated collagen-binding interactions in the minimal affinity range required for stable adhesion. Fluorescence microscopy and immunoblotting showed equivalent amounts of beta1 integrin associated with collagen beads bound to Msp- and vehicle-treated cells. Photobleaching experiments found a similar percentage mobile fraction of beta1 integrins recovered in bleached areas of the plasma membrane. In contrast, Msp-induced inhibition of collagen binding was reversed by beta1 integrin affinity-activating antibodies and by latrunculin B, which prevented subcortical actin assembly. We conclude that native Msp of T. denticola inhibits the binding step of collagen phagocytosis in fibroblasts by inducing subcortical actin filament assembly and restricting affinity modulation of beta1 integrins. We suggest that, like Msp, bacterial toxins that target the cytoskeleton may also perturb the signalling networks required for cellular engagement of matrix ligands.

Actins↗

Ocular manifestations and treatment of syphilis.

Syphilis is a sexually transmitted, chronic, systemic infection caused by the spirochete Treponema pallidum. If left untreated, the disease progresses through four stages, with the potential to cause significant morbidity to any major organ of the body. Frequent syphilitic ocular manifestations, which can occur at any stage of the disease, include interstitial keratitis, anterior, intermediate, and posterior uveitis, chorioretinitis, retinitis, retinal vasculitis and cranial nerve and optic neuropathies. Diagnosis is centered around a high level of clinical suspicion and includes treponemal specific and non-treponemal serologic tests. All patients with newly diagnosed syphilis should be tested for co-infection with human immunodeficiency virus, as the risk factors are similar for both diseases. Additionally, all patients with ocular syphilis should be tested for neurosyphilis. The preferred treatment for all stages of syphilis remains parenteral penicillin G. With proper diagnosis and prompt antibiotic treatment, the majority of cases of syphilis can result in a cure.

Anti-Bacterial Agents↗

Non-plaque-induced gingival lesions.

The origin of gingival inflammation is occasionally different from that of routine plaque-associated gingivitis, and such non-plaque-associated types of gingivitis often present characteristic clinical features. Examples of such forms of gingivitis are specific bacterial, viral, and fungal infections. Specific bacterial infections of gingiva may be due to Neisseria gonorrhea, Treponema pallidum, streptococci, and other organisms. The most important viral infections of gingiva are herpes simplex virus type 1 and 2 and varicella-zoster virus. Fungal infections may be caused by several fungi, the most important of these being Candida species including C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. guillermondii. Gingival histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum and, as for the other specific infections of gingiva, a confirmed diagnosis may require histopathologic examination and/or culture. Atypical gingivitis may also occur as gingival manifestations of dermatological diseases, the most relevant of these being lichen planus, pemphigoid, pemphigus vulgaris, erythema multiforme, and lupus erythematosus. Non-plaque induced gingival inflammation can be caused by allergic reactions to dental restorative materials, toothpastes, mouthwashes, and foods. In addition, gingival inflammation may result from toxic reactions, foreign body reactions, or mechanical and thermal trauma.

Communicable Diseases↗

[Modern syphilis serology. Immunology, tests and their validity].

In the immunological chapter the appearance of the antibodies in several stages of the lues infection and the methods of demonstration are described. With the lipoid-antigen reactions and the antigen-specific tests modern lues serology can give an answer to the three important questions: Exists a lues infection? Is the demonstrated lues infection active? Was the treatment successful? To diagnose a lues infection one should carry out the Treponema Pallidum Haemagglutination (TPHA) test as screening reaction; the Fluorescent Treponemal Antibody Absorption (FTA-Abs) test should be used for confirmation. The quantitative Cardiolipin Microflocculation test (CMT) decides on the activity of the lues infection and can be used to follow up the effectiveness of treatment. In some cases the Treponema Pallidum Immobilization (TPI) test or the demonstration of the 19S-IgM-antibodies must be used for clarification.

Fluorescent Antibody Technique↗

[The pathogenesis of early syphilis with concomitant chlamydiosis].

Migration of Treponema pallidum through the basal membrane to upper layers of the epidermis and destruction of the intercellular junctions (desmosomes) were revealed with the help of electron microscopy of syphilitic chancres. Active phagocytosis of the treponemas by the intraepidermal macrophages (Langerhans cells) and by epidermocytes was shown. Necrosis and apoptosis of the immune cells, basophilic leukocytes degranulation and formation of the cellular symplasts with 3 to 5 lymphocytes were observed more frequently in the case of concomitant Chlamydia trachomatis infection. More vigorous response of the cells of derma on T. pallidum was characteristic of mixed infection (syphilis + chlamydiosis), but elimination of treponemas was not complete.

Adult↗

Serological markers of selected sexually and blood transmitted infections in pregnant women and in newborns of HIV-positive mothers in the Slovak Republic.

Aim of the study was to investigate serological markers of selected sexually and blood transmitted infections (HBV, HCV, CMV, and Treponema pallidum) in the group of pregnant women and in newborns of HIV-positive mothers in Slovakia. IgG antibodies to CMV were found in 78 of 97 women, from them in 6 of 7 HIV-positive and in 72 of 90 HIV-negative persons. Occurrence of HbsAg and HCV was significantly higher in the group of HIV-positive women (1/7 and 2/7) comparing to the HIV-negative one (4/90 and 0/92, respectively). Antibodies to T. pallidum were found only in one HIV-negative woman from 92 women tested. Five of seven children born to HIV-1 infected mothers were found HIV-1 negative, two children are still under control. Four of 7 newborns were found anti-CMV IgG positive. Although one woman, IDU, was confirmed HbsAg and anti-HCV positive, vertical transmission of HBV and HCV to her newborn was not observed by molecular-biological methods. Similarly, HCV antibodies were found in one more women and neither in her child HCV infection was confirmed. In no one of mother - child pair's antibodies to T. pallidum were observed. Due to these findings strong attention should be paid to health education and prophylaxis of mother to child HIV and other STIs transmission in Slovakia.

Antibodies, Bacterial↗

Pattern of sexually transmitted diseases in a Malagasy population.

BACKGROUND: Data concerning the spectrum and antimicrobial susceptibility of STDs in Madagascar are scarce. OBJECTIVES: Improvement of STD patient management in Madagascar. GOAL OF THE STUDY: Assessment of the spectrum of STDs and improvement of therapy. STUDY DESIGN: Etiologic study of 400 patients (169 men, 231 women) under consultation at the major STD service in Antananarivo for one or more of the STD syndromes, urethral discharge, cervicovaginal discharge, genital ulcers, or condylomata according to a fixed diagnostic schedule. RESULTS: Of genital ulcers, syphilis accounted for 46%, lymphogranuloma venereum for 24%, chancroid for 16%, and herpes for 1%. Of the syphilis cases, 51% presented as condyloma lata. Discharge was found in 124 men and 210 women. Counting concomitant infections separately, gonorrhea occurred in 69% of the men and 20% of the women with discharges, chlamydia infection in 42% and 52%, trichomoniasis in 9% and 31%, candidiasis in 12% and 30%. Bacterial vaginosis was found in 37% of the women with discharges. In 32% of male and 71% of female gonorrhea cases, there was concurrent chlamydia infection. Infection with HIV 1 or 2 was not detected. Determination of the antibiotic susceptibility of Neisseria gonorrhoea revealed high efficacy of ampicillin, ciprofloxacin, and spectinomycin; but frequent resistance to tetracycline and cotrimoxazole. CONCLUSIONS: High priority should be given to the management of infections with chlamydia and with Treponema pallidum as well as to educational measures to increase awareness of genital ulcer disease.

Adolescent↗

Immunofluorescent staining of Treponema pallidum and Treponema pertenue in tissues fixed by formalin and embedded in paraffin wax.

The main problems in identifying Treponema pallidum in tissues are optical definition contrast, and specificity. In general, fluorochrome staining provides optical definition and contrast superior to that obtained by ordinary tinctorial staining, and in theory improved resolution. Specificity is lacking however, as with other stains. In contrast, immunofluorescence should combine the optical advantages of fluorochrome staining with the immunological advantages of specificity. Since the validity of such staining depends in part upon the integrity of the antigenic components of the micro-organisms, it is customary to avoid such drastic procedures as are involved in routine fixation and paraffin embedding. The manipulation, however, of unfixed cryostat material, in contrast with that of paraffin sections suffers from two disadvantages--namely, friability and infectivity. Published and unpublished work has shown antigenic stability in T. pallidum to a variety of procedures, both physical and chemical. Consideration of these facts led in this work to successful immunofluorescent staining after routine formalin fixation and paraffin embedding of tissues infected with T. pallidum or Treponema pertenue. Optical definition and contrast, were superior to that obtained with silver methods, but it was not possible to differentiate between these two organisms. Nevertheless immunofluorescence applied as described to paraffin sections should supply a convenient safe, and sensitive means of reappraising the histopathology of treponemal disease in patients, necropsy material, and experimental animals.

Animals↗

Cross-reactivity between B. burgdorferi and other spirochetes affects specificity of serotests for detection of antibodies to the Lyme disease agent in dogs.

Western immunoblots, the kinetics-based enzyme-linked immunosorbent assay (KELA), and the microagglutination test were used to evaluate cross-reactivity among antibodies to serovars of Leptospira interrogans (leptospiral serovars), and B. burgdorferi from naturally infected dogs, and to Serpulina (Treponema) hyodysenteriae from vaccinated rabbits. Whole-cell lysates from Borrelia spp., leptospiral serovars, and Serpulina spp. were used for SDS-PAGE, western blots, and KELA. Crossreactivity occurred between the antibodies to B. burgdorferi and leptospiral serovars when tested on the heterologous antigens. Antibodies to leptospiral serovars tended to cross-react more strongly with antigens of B. burgdorferi spp. than did antibodies to B. burgdorferi when tested against antigens of leptospiral serovars. The antibodies against B. burgdorferi showed a lesser degree of cross-reactivity to the antigens of S. hyodysenteriae and S. innocens than they did to leptospiral serovars. We conclude that cross-reactivity occurs between B. burgdorferi and leptospiral serovars. Validation and interpretation of ELISA tests for detection of antibody activity to whole cell lysates of the Lyme agent must take this cross-reactivity into consideration. Conversely, dogs infected with the Lyme agent do not show significant cross-reactivity in the microagglutination test for antibody to the leptospiral serovars.

Agglutination Tests↗

Diagnosis of neurosyphilis in patients infected with human immunodeficiency virus type 1.

Establishing the diagnosis of neurosyphilis may be particularly difficult in human immunodeficiency virus type 1 (HIV)-infected persons. Polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in cerebrospinal fluid (CSF) from 81 HIV-infected patients. On the basis of reactive serum and CSF-VDRL tests, 2 patients were diagnosed as having neurosyphilis. T. pallidum DNA was not consistently detected in any sample, even when the CSF-VDRL was reactive. CSF pleocytosis, elevated protein, or depressed glucose concentration was not significantly associated with a history of exposure to or infection with T. pallidum. On the basis of results of routine CSF measurements and T. pallidum PCR results, no evidence was found for undiagnosed neurosyphilis in HIV-infected patients. T. pallidum DNA PCR on CSF did not provide more information than conventional CSF analysis. Further study is needed to determine the utility of this test in the diagnosis and treatment of neurosyphilis.

DNA, Bacterial↗

Carbon sources utilized by virulent Treponema pallidum.

Carbon sources utilized by virulent Treponema pallidum organisms extracted from infected rabbit tissue have been investigated. Utilization of 14C-labeled compounds by T. pallidum was monitored by degradation of these compounds to 14CO2. Experiments have consistently shown that of 22 carbon sources examined, [14C]glucose and [14C]pyruvate are selectively degraded to 14CO2 under the experimental conditions employed. When [1-14C]pyruvate, [2-14C]pyruvate, and [3-14C]pyruvate are tested, virulent T. pallidum preferentially degrade and release the carboxyl group as 14CO2. End product analyses indicate that CO2 and acetate are the major products of pyruvate degradation by T. pallidum.

Acetates↗

Identification of four new prokaryotic bacterioferritins, from Helicobacter pylori, Anabaena variabilis, Bacillus subtilis and Treponema pallidum, by analysis of gene sequences.

The nucleotide (nt) sequence of the Helicobacter pylori (Hp) napA gene, encoding neutrophil-activating protein A (HPNAP) was determined. Alignment of this sequence with those of known bacterioferritins (Bfr) revealed sequence homology and conservation of a 7-amino-acid (aa) motif constituting the ferroxidase (Frx) center of Bfr in the HPNAP. The N-terminal aa sequence deduced from the iron-regulated mrgC gene of Bacillus subtilis [Chen et al., J. Bacteriol. 175 (1993) 5428-5437] is highly similar to that of HPNAP and contains five Frx center aa residues. The deduced aa sequences for proteins of unknown function in Treponema pallidum [Walfield et al., Infect. Immun. 57 (1989) 633-635] and in the cyanobacterium Anabaena variabilis [Sato, GenBank accession No. JU0384 (1991)] identify these two proteins as Bfr. Although the DNA-binding protein from starved cells of Escherichia coli [Almiron et al., Genes Dev. 6 (1992) 2646-2654] is clearly a HPNAP/Bfr homologue, a significant part of its Frx center is missing. It is unlikely that the intracellular function of HPNAP is related to its ability to activate neutrophils.

Amino Acid Sequence↗

Porphyromonas gingivalis heat shock protein vaccine reduces the alveolar bone loss induced by multiple periodontopathogenic bacteria.

OBJECTIVES: Heat shock protein (HSP) can be utilized as a vaccine to cross-protect against multiple pathogenic species. The present study was performed to evaluate Porphyromonas gingivalis heat shock protein 60 (HSP60) as a vaccine candidate to inhibit multiple bacteria-induced alveolar bone loss. MATERIAL AND METHODS: Recombinant P. gingivalis HSP60 was produced and purified from P. gingivalis GroEL gene. Rats were immunized with P. gingivalis HSP60, and experimental alveolar bone loss was induced by infection with multiple periodontopathogenic bacteria. RESULTS: There was a very strong inverse relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG) levels and the amount of alveolar bone loss induced by either P. gingivalis or multiple bacterial infection (p=0.007). Polymerase chain reaction data indicated that the vaccine successfully eradicated the multiple pathogenic species. CONCLUSIONS: We concluded that P. gingivalis HSP60 could potentially be developed as a vaccine to inhibit periodontal disease induced by multiple pathogenic bacteria.

Actinobacillus Infections↗

Eradication of some infectious pig diseases by perinatal tiamulin treatment and early weaning.

From 10 days before the expected date of farrowing onwards, 97 sows infected by Mycoplasma hyopneumoniae and Treponema hyodysenteriae were given tiamulin daily at a dosage of 20 mg/kg bodyweight via the feed. Three days before farrowing the sows were washed with a disinfectant and transferred to an isolated farrowing house. The sucking piglets remained with their dams for five days, during which time the sows continued to receive the tiamulin-containing feed. The sucking piglets also received tiamulin daily at a dosage of 30 mg/kg bodyweight. At six days old the weaker piglets of the litter were returned to the original herd, together with their dams. A total of 574 piglets of about 1.5 kg bodyweight each were transferred to an isolated and previously disinfected pig farm and reared there. A total of 13.8 per cent of these pigs died by 50 days old. On the isolated farm, 10.9 per cent of the 829 second generation piglets born to the 101 first generation sows, died up to the age of 50 days. On the isolated farm about 2000 pigs were subjected to repeated clinical, pathological and laboratory examinations for M hyopneumoniae, T hyodysenteriae, Aujeszky's disease virus and Leptospira species during the three year period of study. No evidence of infection with any of these agents was found in the 2000 pigs of the isolation herd, although the original sow herd had been latently infected by these pathogens. No maternally derived antibodies against these pathogens were detectable in sera of three-day-old sucking piglets of the second and third generations.

Administration, Oral↗

[Meningitis in subjects with human immunodeficiency virus infection].

BACKGROUND: Neurological complications are frequently observed in HIV-1 patients. Lumbar puncture (LP) and LSF analysis are two key diagnostic procedures. AIM: To describe the etiology meningeal syndromes in a hospital series of HIV patients. RESULTS: In this study, we present the different meningeal complications from 198 HIV-1 patients referred, for the last five years, to the HIV Center of the Hospital of University of Chile. The diagnosis of HIV-1 was done clinically plus a positive ELISA test, and confirmed by Western blot and/or PCR. In all cases with a possible neurological complication (52/198), a LP was performed. Cytochemical and microbiological studies, were done in each CSF sample. Serum CD4/CD8 lymphocytes number were determined by flow cytometry, and brain CT scan and/or MRI were obtained. From the 52 patients in whom a LP was done, 24 showed an abnormal CSF, compatible with the diagnosis of meningitis. The most frequent etiology (11/24) was infection by Cryptococcus neoformans, followed by Treponema pallidum (7/24). There were 3 cases of HIV-1 meningitis, and 3 other cases with lymphoma, varicella zoster and cytomegalovirus meningitis. The frequency of cryptococcal infection was similar to that reported in the literature, but two interesting observations were the high frequency of neurosyphilis and the absence of TBC meningitis. In our country, the VDRL/FTA-ABS serum tests are mandatory in HIV patients. If these tests were positive a LP was performed, and this could partially explain the high number of cases coinfected with neurosyphilis. There is an important prevalence of lung TBC in our country, and as a consequence there is a policy of immunization to all newborn. It is possible that the high prevalence of TBC "promotes" a more actively search for TBC infection, with an early diagnosis and treatment of pulmonary TBC, and so a more frequent prophylaxis therapy in HIV patients, without the development of TBC meningitis.

Adult↗

A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.

BACKGROUND: Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis. METHODS: In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid. The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up. RESULTS: From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations. The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status. Serologically defined treatment failures were more common among the HIV-infected patients. The single clinically defined treatment failure was in an HIV-infected patient. Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy). T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested. None had clinically evident neurosyphilis, and the rate of detection of T. pallidum did not differ according to HIV status. CONCLUSIONS: After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

Adult↗

Antigenic cross-reactivity between Treponema pallidum and other pathogenic members of the family Spirochaetaceae.

The antigenic cross-reactivity between Treponema pallidum and several pathogenic members of the family Spirochaetaceae was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques. Blots of T. pallidum antigens were incubated with antiserum from rabbits infected or immunized with T. pallidum, Treponema paraluiscuniculi, Treponema hyodysenteriae (strains B204 and T22), Borrelia hermsii serotype 7, or Leptopsira interrogans serogroup Canicola. T. pallidum contained 22 antigenic molecules ranging from 85,000 to 12,000 daltons which were recognized by serum from rabbits infected with T. pallidum. Serum from rabbits infected with T. paraluiscuniculi cross-reacted with 21 of these molecules and faintly reacted with a band at 15,000 daltons which was not recognized by anti-T. pallidum serum. Antisera directed against strains B204 and T22 of T. hyodysenteriae cross-reacted with 11 and 10 antigens of T. pallidum, respectively. B. hermsii and L. interrogans serogroup Canicola antisera detected 11 and 10 treponemal antigens, respectively. Many of the T. pallidum antigens detected by antisera against T. hyodysenteriae, B. hermsii, or L. interrogans serogroup Canicola have been previously identified as containing moieties also found on the nonpathogenic Treponema phagedenis, biotype Reiter, and may therefore represent group antigens common to members of the family Spirochaetaceae.

Animals↗

[Renal toxicity in HIV-infected patients receiving HAART including tenofovir].

HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal disease before starting an antiretroviral regimen including tenofovir is necessary to prevent renal damage. Furthermore, frequent monitoring of renal function in patients at higher risk of renal damage is strongly recommended, as well as a tenofovir dose adjustment if an alteration of renal function is detected.

Adenine↗