Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an Airway Infection in Mice.

is a cause of high mortality in burn, immunocompromised, and surgery patients. High incidence of antibiotic resistance in this pathogen makes the existent therapy inefficient. Type three secretion system (T3SS) is a leading virulence system of that actively suppresses host resistance and enhances the severity of infection.

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity against Intravaginal Infection.

imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae.

A small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones suppresses Salmonella infection in vivo.

Therapeutic strategies that target bacterial virulence have received considerable attention. The type III secretion system (T3SS) is important for bacterial virulence and represents an attractive therapeutic target. A novel compound with a predicted T3SS inhibitory activity named CL-55 (N-(2,4-difluorophenyl)-4-(3-ethoxy-4-hydroxybenzyl)-5-oxo-5,6-dihydro-4H-[1,3,4]-thiadiazine-2-carboxamide) was previously characterized by low toxicity, high levels of solubility, stability and specific efficiency toward Chlamydia trachomatis in vitro and in vivo.

A small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones inhibits intracellular growth and persistence of Chlamydia trachomatis.

Chlamydia trachomatis is one of the most common sexually transmitted pathogens in the world and often causes chronic inflammatory diseases that are insensitive to antibiotics. The type 3 secretion system (T3SS) of pathogenic bacteria is a promising target for therapeutic intervention aimed at bacterial virulence and can be an attractive alternative for the treatment of chronic infections. Recently, we have shown that a small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones produced through the chemical modification of the thiohydrazides of oxamic acids, designated CL-55, inhibited the intracellular growth of C.

Small molecule inhibitor of type three secretion suppresses acute and chronic Chlamydia trachomatis infection in a novel urogenital Chlamydia model.

Previously, we reported that a compound from a group of thiohydrazides of oxamic acids, CL-55, possessed antichlamydial activity in vitro that was accompanied by a decreased translocation of the type three secretion effector, IncA, into the host cell. In this study, the antichlamydial activity of CL-55 was tested in vivo in DBA/2 mice infected with C. trachomatis serovar D.

[Use of immunological and molecular biological methods to diagnose cerebral toxoplasmosis in HIV infection].

Cerebral toxoplasmosis is one of the leading causes of neurologic diseases with high mortality rates in patients with HIV infection. Invasion was difficult to diagnose for a number of objective reasons. The objective of the investigation was to determine the clinical sensitivity of different laboratory techniques as both a single study and their various combinations to verify the diagnosis of cerebral toxoplasmosis in HIV-infected patients.

Roquefort cheese proteins inhibit Chlamydia pneumoniae propagation and LPS-induced leukocyte migration.

Inflammation in atherosclerosis, which could be associated with some subclinical infections such as C. pneumoniae, is one of the key factors responsible for the development of clinical complications of this disease. We report that a proprietary protein extract isolated from Roquefort cheese inhibits the propagation of C.

[Toxoplasmosis in HIV infection: invasion reactivation criteria].

Contemporary representation of toxoplasmosis reactivation criteria in HIV infection is generalized. Significance of the issue is justified: toxoplasmosis is a leading neurological pathology in AIDS with a high lethality percentage due to complexity of clinical confirmation and difficulties of laboratory confirmation of the start of reactivation. Clinical, instrumental, immunologic, molecular genetic invasion reactivation criteria are discussed in the article and analysis of their effectiveness is performed; their most feasible combinations are justified.

[Characteristic of early mucosal immune response in mice during intravaginal infection caused by Chlamydia muridarum].

Aim: Comparison of features of recruitment to infection focus of cells mediating early immune reactions in intravaginally infected mice that had previously received or not received covinan (progesterone analogue).

Materials And Methods: A/Sn and BALB/c line mice were used in the study. C.

[Model of chronic salmonellosis: parameters of infection and immune response in inbred mice genetically variable in susceptibility to salmonellosis].

Aim: Study parameters of chronic infection and immune response in I/St and A/Sn line mice in the model of per oral infection of mice with Salmonella enterica serovar Typhimurium.

Materials And Methods: Studies were carried out in I/StSnEgYCit (I/St), A/JsnYCit (A/Sn) inbred line mice as well as their back crossing hybrids [I/StrxF1(I/StxA/Sn)]BC. Mice were infected per os by S.

[Features of epidemiology and diagnostics of toxoplasmosis during HIV-infection].

Aim: Comparative assessment of effectiveness of serologic methods for toxoplasmosis diagnostics in patients with HIV-infection.

Materials And Methods: Sera and CSF samples from 166 patients with AIDS stage IIIB were tested for antibodies to Toxoplasma gondii by indirect immunofluorescence, ELISA and immunoblotting. Results of serological tests were compared with clinical, pathological data as well as with results of MRI and PCR.

[Study of persistence of low virulent strain of Toxoplasma gondii on in vivo model].

Aim: To study virulence of Toxoplasma gondii strain isolated from pathologicoanatomic brain tissue of HIV-infected patients on in vivo model as well as immune response to the pathogen in immunocompetent animals and in animals with cyclophosphamide-induced areactivity.

Materials And Methods: Groups of immunocompetent and immunodeficient mice were inoculated with cysts of T. gondii obtained from brain tissues of deceased HIV-infected patients.

Functional activity of peritoneal macrophages from sensitive and resistant mouse strains during intravaginal infection with herpes simplex virus type 2 and mucosal vaccination.

In the early period after intravaginal infection with herpes simplex virus type 2 (2 h), macrophages from sensitive DBA/2 mice were characterized by higher capacity to engulf the antigen, decreased function of the lysosomal apparatus, lower activity of cathepsin D, and reduced oxygen metabolism compared to cells from resistant BALB/c mice. Mucosal vaccination with herpes vaccine and hyaluronic acid promoted the increase in functional activity of macrophages and improved survival of sensitive mice (by 60%).

[Cryptosporidiosis: current views of its pathogenesis and resistance].

Cryptosporidiosis is a socially dangerous opportunistic infection that is intractable and, according to recent data, caused by a diversity of species of the genus Cryptosporidium, which are still recently considered to be nonpathogenic to a human being. The transmission of this infection is by the water route and the technology of water purification cannot be saved from the oocysts of Cryptosporidium. Therefore, the important line of investigations is to study the immunological aspects of the interaction of Cryptosporidia with the cells of a microorganism, the development of a pathological process, and the persistence of the pathogen.

Comparative study of macrophage response in mice after DNA immunization and infection with herpes simplex virus type 1.

Functional activity of macrophages and intensity of T cell immune response in mice were studied after intravaginal and intraperitoneal infection with herpes simplex virus type 1 and DNA vaccination in combination with adjuvant treatment (recombinant granulocyte-macrophage colony-stimulating factor and glucosaminylmuramyl dipeptide). DNA vaccination induced a virus-specific T cell immune response with no macrophagic inflammatory reaction. Infection with herpes simplex virus type 1 was accompanied by sustained inflammation, but not by the T cell immune response.

An investigation of the ability of orally primed and tolerised T cells to help B cells upon mucosal challenge.

The oral delivery of soluble antigens induces unresponsiveness to systemic challenge that can be demonstrated as a reduced ability of tolerised T cells to support B-cell expansion and antibody production. However, it remains controversial whether previously induced oral tolerance results in suppression or priming, or has no effect on B-cell responses upon oral challenge. Using a double adoptive transfer system, we primed or tolerised T cells (independently of B cells) with a high dose of fed antigen, and examined the ability of these primed or tolerised T cells to support B-cell clonal expansion in response to orally delivered conjugated antigen.

Tracking lymphocytes in vivo.

The ability to track antigen (Ag)-specific lymphocyte populations in vivo has greatly increased our understanding of the location and functional status of these cells throughout the course of an immune response. Recent technical advances have enhanced researchers' capability to follow migration, activation and cellular interactions of Ag-specific lymphocytes in situ. It is now possible to monitor changes in T cell subsets, co-stimulatory molecules, and chemokine expression within the physiological context of secondary lymphoid organs.

An investigation of the distribution of antigen fed in tolerogenic or immunogenic forms.

It remains unclear which cells present fed antigen and whether their phenotype and/or activation state differs between oral tolerance and priming. Furthermore, it is also controversial whether the presentation occurs locally in the gut and/or systemically. Clarifying these issues will be important for the design and use of oral vaccines, the therapeutic use of oral tolerance and understanding of IBD.

A reporter system for prokaryotic and eukaryotic cells based on the thermostable lichenase from Clostridium thermocellum.

The coding region of the licB gene from Clostridium thermocellum was truncated at the 3' end. The modified lichenase encoded by the construct (LicBM2) retained the most important properties of the enzyme - its high activity and thermostability. LicBM2 consists of the catalytic domain and part of the Pro-Thr-box.

Preparation and properties of Clostridium thermocellum lichenase deletion variants and their use for construction of bifunctional hybrid proteins.

Major properties (pH and temperature optimum, stability) of lichenase (beta-1,3-1,4-glucanase) deletion variants from Clostridium thermocellum were comparatively studied. The deletion variant LicBM2 was used to create hybrid bifunctional proteins by fusion with sequences of the green fluorescent protein (GFP) from Aequorea victoria. The data show that in hybrid proteins both GFP and lichenase retain their major properties, namely, GFP remains a fluorescent protein and the lichenase retains activity and high thermostability.

Characterization of T cell clones derived from lymph nodes and lungs of Pseudomonas aeruginosa-susceptible and resistant mice following immunization with heat-killed bacteria.

Pseudomonas aeruginosa-resistant BALB/c and susceptible C57Bl/6 (B6) mice were immunized with heat-killed Pseudomonas either in the foot pad or via the trachea, and panels of Pseudomonas-specific T cell clones were developed from lymph nodes and lungs. All clones from either strain, whether of lymph node or lung origin, were CD3+CD4+CD8-TCRalphabeta+. The efficacy of cloning from lymph node cells was comparable between BALB/c and B6 mice.