Antibiotic Adjuvant 4-Hexylresorcinol Enhances the Efficiency of Antituberculosis Drugs.

We studied the possibility of using 4-hexylresorcinol to increase the efficiency of anti-mycobacterial chemotherapy. In an in vitro experiment, 4-hexylresorcinol increased the efficiency of rifampicin, kanamycin, and isoniazid against Mycobacterium smegmatis by 3-5 times. Experiments in sanitation of BALB/c mice infected with M. smegmatis showed the best efficacy of the isoniazid and 4-hexylresorcinol combination in comparison with isoniazid monotherapy. The growth-inhibiting activity of the combination of antibiotic rifabutin with 4-hexylresorcinol was shown on 6 strains of M. tuberculosis. A 2-fold decrease in the minimum inhibitory concentration of this antibiotic in the presence of half-minimum inhibitory concentration of 4-hexylresorcinol was demonstrated for monoresistant strain M. tuberculosis 5360/42Hr. On the mouse model of experimental tuberculosis caused by M. tuberculosis H37Rv, a 5-fold decrease in lung contamination and more rapid complete cure were achieved in animals treated with the combination of rifabutin and 4-hexylresorcinol in comparison with rifabutin monotherapy.

Pseudomonas aeruginosa efflux pump superfamily (review of literature).

The significant increase in the number of antibiotic-resistant microorganisms observed in recent years is a public health problem worldwide. One of the molecular mechanisms for the formation of antimicrobial resistance in bacteria is the presence of efflux pumps. The review presents an analysis of experimental studies related to the study of efflux pumps in clinical strains of Pseudomonas aeruginosa, one of the representatives of hospital pathogens of the ESKAPE group. This review is intended for specialists developing new types of drugs against antibiotic-resistant strains, as well as researchers studying the mechanisms of bacterial resistance to antibiotics, heavy metals, biocides and other antimicrobial factors.

[In vitro models of Mycobacterium tuberculosis dormancy, and in vivo models of latent tuberculosis infection.]

Modeling of tuberculosis infection is carried out in order to clarify various aspects of the tuberculosis pathogenesis, as well as the testing of new anti-tuberculosis drugs. The characteristic of in vitro models (n = 16) for Mycobacterium tuberculosis dormant state and in vivo models (n = 14) for the latent tuberculosis infection involving several animal species published to date are presented in this review. A brief description of the models and the results obtained by the authors are presented. The analysis of the published data reflects the list of methodological procedures that allow researchers to study the mechanism of the transition of M. tuberculosis cells to a dormant state and reverse to metabolically active state, as well as the process of conversion of active tuberculosis infection to a latent tuberculosis and reactivation.

Multi-subunit BCG booster vaccine GamTBvac: Assessment of immunogenicity and protective efficacy in murine and guinea pig TB models.

New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models. Results show that in both infectious models, GamTBvac has a strong immunogenicity and significant protective effect against Mycobacterium tuberculosis strain H37Rv under aerosol and intravenous challenges. GamTBvac showed a particularly strong protective effect as a BCG booster vaccine.

[Specific features of minute structure of Mycobacteria cultured in murine macrophages]. / Osobennosti tonkoi struktury mikobakterii tuberkuleza, kul'tivirovannykh v makrofagakh myshi.

In experimentally infected murine peritoneal macrophages and murine macrophage-like cells J-774 with different pathogen strains of tuberculos'is, Mycobacterium tuberculosis (MBT) underwent significant morphofunctional changes. In phagocytosis, several live and mycobacteria conventionally referred by the authors to as morphotype I cells come from the environment to the macrophage. Of them, single young and intact mycobacteria are able to multiply and form at 2-3 generations morphotype II microcolonies from 3-9 mycobacteria or more in the phasolysosomes within the first 24 hours after infection. Having taken the form of small-sized cocci and coccoovals having a closely packed cytoplasm, morphotype II cells can be long present intact in the phagocytes. By losing the cellular wall under the action of lytic phagolysosomal enzymes, single mycobacteria turned into L-form or morphotype III MBT. During damage and lysis in the macrophages, single mycobacteria can preserve a part of an intact cytoplasm and genome as ultraminor forms of mycobacteria or morpho-type IV MBT.

[Effect of fosfidomycin on development of various infections in mice]. / Deistvie fosmidomitsina na razvitie nekotorykh infektsii u myshei.

Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.

[Immunomodulatory properties of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate and search for its new derivatives]. / Immunomoduliatornye svoistva i poisk novykh proizvodnykh 2-C-Metil-D-éritriol-2,4-tsiklopirofosfata.

A strong immunomodulatory effect of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEC) responsible for the survival of bacteria was shown on isolated macrophages and in experimental infections in mice (typhoid and tularemia). Derivatives of MEC were found by 1H-NMR spectroscopy under stress conditions in colorless mutants of the bacteria and isolated to be subsequently purified and used for modulation of the immune system of animals.

[The physicochemical and biological characteristics of the Yersinia pestis pH 6 antigen isolated by an immunosorption method]. / Fiziko-khimicheskaia i biologicheskaia kharakteristika pH6-antigena Yersinia pestis, vydelennogo immunosorbtsionnym metodom.

The immunosorption method was shown to be suitable for the isolation of antigen pH 6, thus making it possible to obtain a highly active preparation. As eluent, 3.0 M KSCN was used. According to the data of gel filtration, the molecular weight of purified antigen pH 6 exceeds 1 x 10(6) daltons. In SDS disk electrophoresis antigen pH 6 is segregated into subunits of approximately 130,000 daltons. The preparation induces inflammatory reaction if introduced intradermally and possesses hemagglutinating and cytotoxic activity.