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Sotnikov D.V.,RAS A.N. Bach Institute of Biochemistry | Zherdev A.V.,RAS A.N. Bach Institute of Biochemistry | Avdienko V.G.,Central Tuberculosis Research Institute | Dzantiev B.B.,RAS A.N. Bach Institute of Biochemistry
Applied Biochemistry and Microbiology | Year: 2015

A new immunochromatographic assay was developed for serodiagnosis of tuberculosis based on the interaction of specific anti-Mycobacterium tuberculosis immunoglobulins that are present in the blood serum with a label-antigen conjugate followed by the binding of the resulting complex to the Staphylococcus aureus protein A immobilized on a test strip. Unlike the conventional technique, in which all immunoglobulins that are present in the sample react with a label-immunoglobulin-binding protein conjugate, the new technique eliminates the binding of blood serum immunoglobulins, which are non-specific to Mycobacterium tuberculosis, to the label, and then specific antibodies involved in the labeled complex bind to the immobilized antigen. The new assay was implemented using the recombinant 38-kDa (Rv0934) protein of M. tuberculosis as the antigen and colloidal gold as the label. It was experimentally shown that the new assay allows for an increase in the percentage of the detection of seropositive serum samples with low concentrations of specific antibodies against the causative agent of tuberculosis. © 2015, Pleiades Publishing, Inc. Source


Lyubimov S.E.,RAS Nesmeyanov Institute of Organoelement Compounds | Ozolin D.V.,RAS Nesmeyanov Institute of Organoelement Compounds | Ivanov P.Y.,RAS Nesmeyanov Institute of Organoelement Compounds | Maiorov K.B.,Central Tuberculosis Research Institute | And 2 more authors.
Russian Chemical Bulletin | Year: 2015

A direct iridium-catalyzed asymmetric reductive amination of ketones using an amidophosphite ligand was accomplished for the first time. A new one-step approach to the preparation of biologically active pyrazinocarbazoles was developed. © 2015 Springer Science+Business Media, Inc. Source


Day T.A.,Max Planck Institute for Infection Biology | Day T.A.,Seattle Biomedical Research Institute | Koch M.,Max Planck Institute for Infection Biology | Koch M.,Bayer AG | And 13 more authors.
European Journal of Immunology | Year: 2010

Tuberculosis causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associatedwith pulmonary granuloma are observed during tuberculosis in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO) were infected with Mycobacterium tuberculosis (MTB). As in WT mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated in the absence of SLO. Moreover, adoptively transferred T cellswere primed locally in lungs in a granuloma-dependent manner. T-cell activation was delayed in the absence of SLO, but resulted in a normal development program including protective subsets and functional recall responses that protected mice against secondary MTB infection. Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. Source


Duque-Correa M.A.,Max Planck Institute for Infection Biology | Kuhl A.A.,Max Planck Institute for Infection Biology | Rodriguez P.C.,Charite - Medical University of Berlin | Zedler U.,Max Planck Institute for Infection Biology | And 10 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -unin-fected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via L-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes L-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granu-loma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hyp-oxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia. Source


Matyugina E.,RAS Engelhardt Institute of Molecular Biology | Novikov M.,Volgograd State University | Babkov D.,Volgograd State University | Ozerov A.,Volgograd State University | And 10 more authors.
Chemical Biology and Drug Design | Year: 2015

Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, and 1,3-di-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4⌄-hydroxy-2⌄-cyclopenten-1⌄-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymatic target. Three series of 5-arylaminouracil derivatives were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the M. tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4⌄-hydroxy-2⌄-cyclopenten-1⌄-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). © 2015 John Wiley & Sons A/S. Source

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