295 results about "Tuberculosis Disease" patented technology

The invention discloses an application of cryptotanshinone in preparation of an anti-mycobacterium tuberculosis drug, and relates to the technical field of bioengineering. The molecular formula of the valerianin disclosed by the invention is C19H20O3. The mycobacterium tuberculosis is a mycobacterium tuberculosis H37Rv strain. Cryptotanshinone is disclosed as a natural-source compound for the first time, has the dual advantages of high efficiency and low toxicity, has an obvious effect of resisting mycobacterium tuberculosis, provides a brand new candidate drug scheme with development potential for solving the difficulty of tuberculosis treatment, and has great scientific value and application prospect.

The invention belongs to the field of biological medicine, and relates to a tuberculosis molecular marker combination and application thereof. Specifically, the invention relates to a molecular marker combination, which comprises (A) nucleic acid for coding GLRX protein, and one or more of nucleic acid for coding FCGR1A protein, nucleic acid for coding IFITM1 protein and nucleic acid for coding UBE2L6 protein; or (B) a GLRX protein, and one or more selected from the group consisting of an FCGR1A protein, an IFITM1 protein, and a UBE2L6 protein. The molecular marker combination can effectively diagnose the active tuberculosis or effectively distinguish the active tuberculosis from latent tuberculosis infection and normal control, and has high sensitivity and specificity.

Provided herein are nucleic acid vaccine constructs comprising synthetic polynucleotides encoding a Mycobacterium tuberculosis (Mtb) RelA-SpoT homolog (RSH) protein, RelMtb, or a functional portion, fragment, or variant thereof, conjugated to a macrophage inflammatory protein-3 alpha (MIP-3α) or other chemokine that binds to a chemokine receptor 6 (CCR6), or a functional portion, fragment, or variant thereof, or to an antibody, or antigen binding portion thereof, that binds to a CCR6. Methods for making the vaccine constructs and their use in prophylaxis and treatment of Mtb infections are also provided.

The invention belongs to the field of tuberculosis diagnosis, and particularly relates to an application of a KNCN recombinant protein in tuberculosis diagnosis. The KNCN recombinant protein can specifically and efficiently capture various tuberculosis antigens, the KNCN protein can capture several tuberculosis antigens in a tuberculosis patient specimen at the same time, and by expressing and purifying the recombinant KNCN protein, the captured binding antigen is detected.

The invention discloses identification and application of a mycobacterium tuberculosis bacteriophage susceptibility gene, and a gene target which affects mycobacterium bacteriophage infection efficiency is obtained through combined application of a mycobacterium tuberculosis CRISPR-KO library and a CRISPRi library and bacteriophage D29 infection screening. Reagents or drugs targeting phage susceptibility genes or encoded proteins thereof are screened based on the gene targets, and the reagents or drugs can knock out the phage susceptibility genes or inhibit expression of the phage susceptibility genes, or inhibit activity of the encoded proteins of the phage susceptibility genes, serve as phage synergists, or are combined with antibiotics to be used with phages, and can be used for preparing drugs for treating the phage susceptibility genes or the encoded proteins of the phage susceptibility genes. The bacteriophage-antibiotic composition has the advantages that a synergistic sterilization effect is achieved, a new strategy is provided for bacteriophage-antibiotic combined treatment of drug-resistant mycobacterium infection, rapid sterilization is expected to be achieved, the treatment course is shortened, and finally the target of rapid treatment of tuberculosis and other pathogenic mycobacterium infection is achieved.

The invention discloses a sheep paratuberculosis specific detection kit and application, and relates to the field of biological detection.The kit comprises an elisa plate coated with a recombinant Mycobacterium paratuberculosis membrane protein antigen, the nucleotide sequence of the recombinant Mycobacterium paratuberculosis membrane protein antigen is shown as SEQ ID NO: 1, and the amino acid sequence of the recombinant Mycobacterium paratuberculosis membrane protein antigen is shown as SEQ ID NO: 2; a confining liquid; a serum diluent; carrying out enzyme labeling on a second antibody; a TMB color developing solution and a stop solution; according to the sheep paratuberculosis specific detection kit disclosed by the invention, the recombinant Mycobacterium paratuberculosis membrane protein antigen is adopted as a core detection component, and the antigen has high specificity and can accurately identify paratuberculosis positive serum and effectively distinguish positive and negative samples; meanwhile, prokaryotic expression and purification are carried out on the specific membrane protein of the mycobacterium paratuberculosis for the first time, and a novel sheep paratuberculosis indirect ELISA diagnosis method with high sensitivity and specificity based on the protein as an antigen is established.

The invention provides sgRNA for detecting tuberculosis based on an RPA-CRISPR Cas12b technology, a kit, a detection method and application, and belongs to the technical field of molecular detection. The invention provides sgRNA (single guide ribonucleic acid) for detecting mycobacteria. The sgRNA comprises sgRNA-6110 of which the nucleotide sequence is shown as SEQ ID NO: 1 and / or sgRNA-1081 of which the nucleotide sequence is shown as SEQ ID NO: 2. The sgRNA provided by the invention can specifically recognize and combine high-conservative-degree target sequences IS6110 and IS1081 of mycobacterium tuberculosis and / or mycobacterium bovis, and can be used for instant test of human and livestock tuberculosis pathogenic bacteria mycobacterium tuberculosis and / or mycobacterium bovis.

The invention provides a tuberculosis mRNA vaccine as well as a preparation method and application thereof. The invention firstly provides an antigen, which comprises the following antigen components: at least one fusion protein or chimeric protein formed by mycobacterium tuberculosis early secretion antigens Ag85A and Ag85B and / or immunocompetence fragments thereof, at least one mycobacterium tuberculosis PE / PPE family antigen Rv1759c (PE-PGRS family protein WAG22) or immunocompetence fragments thereof, and at least one immunocompetence fragment thereof, and at least one mycobacterium tuberculosis latent associated antigen Rv1813c or an immunocompetence fragment thereof; selectively, two or more of these antigens or immunocompetent fragments thereof may form a fusion protein and / or chimeric protein as an antigen component. The mRNA vaccine with multiple antigen components has a more effective effect on prevention of tuberculosis.

The invention discloses an electrochemical biosensor for detecting mycobacterium tuberculosis. The sensor takes a porous membrane as a base material, the inner wall of a pore channel of the porous membrane is co-modified with a polydopamine (PDA) and conductive carbon material composite layer, and an amino-modified specific capture probe based on a mycobacterium tuberculosis ESAT-6 gene is fixed on a modification layer through covalent binding. When a target gene is captured by a probe, the volume effect of the target gene causes blockage of a porous channel of the porous membrane, so that electrochemical signals (such as current) of the sensor are changed, and high-sensitivity and specific detection of mycobacterium tuberculosis is realized. According to the invention, a porous structure, biological probe specific fixation and an electrochemical signal conversion technology are combined, and a novel efficient tool is provided for rapid diagnosis of tuberculosis.

The invention relates to the technical field of biological medicines, in particular to a tuberculosis vaccine antigen and a vaccine. In particular to application of a mycobacterium tuberculosis Rv1787 gene in preparation of a vaccine for preventing and / or treating tuberculosis, in the application, the sequence of the Rv1787 gene or an encoding product thereof is defined, and the Rv1787 gene and the encoding product thereof serve as antigens, have mycobacterium tuberculosis specificity, and can be used for preparing a vaccine for preventing and / or treating tuberculosis. According to the mycobacterium tuberculosis vaccine, identification and response of an organism immune system to mycobacterium tuberculosis can be accurately stimulated, non-specific immune response to other normal tissues is avoided, a brand new and specific molecular target spot is provided for preventing and treating tuberculosis, and the limitation that a traditional vaccine depends on a single antigen or an attenuated strain is broken through. A specific expression product of the gene can stimulate directional recognition and attack of an organism immune system on mycobacterium tuberculosis, the pertinence and effectiveness of vaccines are remarkably improved, and a new path is provided for solving the problem of tuberculosis prevention and treatment.

The present invention provides a clofazimine ethanol crystalline compound, its preparation method, application, and pharmaceutical composition, relating to the field of biomedicine. The clofazimine ethanol crystalline compound provided by the present invention has a small size and a relatively large surface area. When used as a pharmaceutical, it has a high dissolution rate and a high in vivo absorption rate, enabling faster achievement of higher blood drug concentrations and providing enhanced therapeutic effects against diseases such as leprosy and drug-resistant tuberculosis.

The invention belongs to the field of nucleic acid detection, and discloses a method for detecting mycobacterium paratuberculosis based on a CRISPR-Cas12a technology. Aiming at the problems that an existing MAP detection method is time-consuming, high in cost and low in sensitivity and specificity, and an existing CRISPR technology is poor in adaptability, insufficient in detection of low bacterium loading amount and the like, the method is combined with recombinase polymerase amplification (RPA) and nested polymerase chain reaction (PCR), takes an MAP high-conservative genome sequence as a target, and fuses high sensitivity of nucleic acid amplification and high specificity and signal amplification capability of CRISPR-Cas12a (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-CRISPR-CRISPR-CRISPR-CRISPR-CRISPR-Cas12a). The lowest detection limit of the kit reaches 1020M, which is far better than the single use effect of the traditional PCR or CRISPR, and the kit realizes ultra-sensitive, high-specificity, rapid and low-cost detection, and is suitable for paratuberculosis early infection or low-bacterial-loading sample detection.

The present invention provides an electrochemical aptamer sensor for detecting Mycobacterium tuberculosis ESAT‑6 antigen. The sandwich electrochemical biosensor uses a new type of MXene@Hemin‑AuNPs nanozyme as a signal amplifier and N‑CNTs‑AuNPs as a sensing interface to detect the Mycobacterium tuberculosis-specific antigen ESAT‑6 in the serum of tuberculosis patients, providing a new method for the diagnosis of tuberculosis.

Provided here are nucleic acid constructs containing a Mycobacterium tuberculosis genome comprising a mutation (such as a deletion) of the sigH gene (AsigH) and a mutation (such as a deletion) of at least one additional gene, and mutant Mycobacterium tuberculosis encoded by the nucleic acid constructs. Also provided are methods of making such nucleic acid constructs and Mycobacterium tuberculosis mutants, and uses thereof. The construct can stimulate an immune response against Mycobacterium tuberculosis in a subject, and can be used as live attenuated vaccines.

The invention discloses an application of a single base / amino acid mutation of a bovine DDX58 gene in anti-tuberculosis, belongs to the technical field of bovine tuberculosis prevention and treatment, an application of a single base mutation of a bovine DDX58 gene in anti-tuberculosis, the CDS sequence of the bovine DDX58 gene is shown in SEQ ID NO.1, the amino acid sequence is shown in SEQ ID NO.2, and the single base mutation is located at the 11603839th nucleotide from the 5′ end of chromosome 8 of the ARS-UCD1.2 version reference sequence of the bovine genome. The single base mutation of the bovine DDX58 gene provided by the present invention has a significant effect on the production amount of type I interferon and the clearance effect of macrophages on Mycobacterium tuberculosis, and is highly linked to the anti-tuberculosis trait of the bovine; the single base / amino acid mutation of the bovine DDX58 gene provided can be used as a bovine tuberculosis resistance linkage site, used for genotype selection in bovine tuberculosis resistance breeding, thereby simplifying the selection method and shortening the selection time.

Disclosed are an mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one early-secreted antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof; PE / PPE family antigen WAG22 of Mycobacterium tuberculosis or an immunologically active fragment thereof; and at least one latent-related antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which may serve as a prophylactic vaccine for preventing latent activation or as a therapeutic drug for treating active tuberculosis, exhibiting a significant inhibitory effect on Mycobacterium tuberculosis.

The invention discloses a primer composition for detecting drug resistance of mycobacterium tuberculosis, a related product and application, and belongs to the field of pathogen detection. The primer composition comprises a primer pair aiming at an rpoB gene, a primer pair aiming at a katG gene, a primer pair aiming at an inhA gene, a primer pair aiming at an ahpC gene, a primer pair aiming at a gyrA gene and a primer pair aiming at a gyrB gene. According to the invention, mutation of mycobacterium tuberculosis complex and rifampicin, isoniazide and quinolone drug resistance related genes rpoB, katG, inhA, ahpC, gyrA and gyrB genes in sputum of a tuberculosis patient can be detected at one time, single-tube multiple high-sensitivity detection is realized, wild genes and mutant genes are accurately distinguished, and serious cross reaction is avoided.

The present invention relates to novel rufamycin analogs that target the ClpC1 protease. The compounds of the present invention have antibacterial activity, e.g., with anti-tuberculosis properties, and are useful in the treatment of e.g. Tuberculosis.

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; a mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunocompetence fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

Disclosed are compositions and methods for the treatment of tuberculosis and other mycobacterial and gram-positive bacterial infections. These compositions comprise highly potent and selective oxazolidinones encapsulated with high efficiency to maximize the potential for low-toxicity drug delivery and are stable in the presence of plasma. The compositions are long-circulating and retain their encapsulated drug while in circulation following intravenous delivery to allow effective accumulation at the site of bacterial or mycobacterial infection. The high doses achievable and the long-circulating nature of the drug combined with the high stability of the formulation allow for a reduction in the frequency of administration compared to the once-daily or twice-daily administration of other drugs commonly used to treat these infections.

The application belongs to the technical field of biological medicine, and particularly relates to a non-classical IFN-gamma-dependent mycobacterium tuberculosis peptide epitope P15, a coding sequence and application thereof, and an anti-tuberculosis vaccine. The amino acid sequence of the mycobacterium tuberculosis peptide epitope P15 is shown as SEQ ID NO. 1. The application is found through research that the mycobacterium tuberculosis peptide epitope P15 has good immunogenicity, in-vivo immunity has a significant anti-tuberculosis protection effect, and the protection effect is not dependent on the host cell IFN-gamma response, and can be used as an ideal target antigen of a tuberculosis vaccine, and is made into an epitope vaccine, and has a good application prospect.

The present application relates to the technical field of diagnostic markers, in particular to a marker combination and its application in diagnosing active tuberculosis and distinguishing between latent tuberculosis infection and active tuberculosis. The lectin combination provided by the present application can be used as a marker for ATB diagnosis and distinguishing between LTBI and ATB, and has high specificity and sensitivity. The lectin combination provided by the present application in combination with detection of specific antibodies of mycobacterium tuberculosis antigens can further improve the diagnostic effect. The marker and its detection products provided by the present application have good application potential in ATB diagnosis and distinguishing between LTBI and ATB, and are expected to overcome the limitations of existing diagnostic techniques, improve the diagnostic accuracy and sensitivity of tuberculosis, and provide new ideas and technical means for early detection, precise treatment and effective prevention and control of tuberculosis.

The present invention provides a CRISPR system and a kit for detecting drug-resistant tuberculosis, which belong to the technical field of drug-resistant tuberculosis detection. The CRISPR system includes AaCas12b and sgRNA; the sgRNA includes a first sgRNA targeting the tuberculosis-specific sequence IS6110; and also includes a second and a third sgRNA targeting the drug-resistant tuberculosis rpoBS531L and / or katGS315T mutation sites. The present invention is based on the Crispr-AaCas12b system, targeting the tuberculosis-specific sequence IS6110 and the most common mutation sites of drug-resistant tuberculosis. By selecting PAM and adjusting the length of the sgRNA spacer binding region and artificially introducing base mismatches, Crispr-AaCas12b can specifically recognize drug-resistant mutation sites and does not recognize wild-type sequences; drug-resistant tuberculosis is quickly and accurately detected by fluorescence signal monitoring.

The invention relates to a mycobacterium tuberculosis EspB polyclonal antibody as well as a preparation method and application thereof. The purified EspB antibody has good detection specificity, only reacts with mycobacteria, and does not react with other common pneumonia pathogenic bacteria. The EspB polyclonal antibody specifically recognizes mycobacteria EspB, comprises mycobacterium tuberculosis and nontuberculous mycobacteria (NTM) EspB which grows slowly and rapidly, and can be used for detecting tuberculosis and NTM diseases.

The present invention relates to the use of a therapeutic agent based on cell wall fragments of a virulent strain of Mycobacterium tuberculosis-complex for the preparation of a drug for the treatment of patients with active tuberculosis.

FIELD: pharmacology.SUBSTANCE invention can be used to determine the concentration of an anti-tuberculosis drug in blood serum. The method for determining the concentration of bedaquiline in the blood serum in patients with tuberculosis or mycobacteriosis is that whole blood samples are centrifuged at 3000 rpm for 20 minutes, then the blood plasma is collected in sterile 1.5 mL Eppendorf tubes, then 900 mcL of acetonitrile are added to 300 mcL of plasma and centrifuged at 13500g for 15 minutes, then 1 mL of the supernatant is transferred to a chromatographic vial and make the assay by UHPLC MS / MS using an Athena UHPLC C18, 1.8 mcM, 120A, 2.1×100 mm chromatography column, when using an aqueous solution containing 5 g / L of ammonium acetate, 25 ml / L of concentrated acetic acid, 2 ml / L trifluoroacetic acid as mobile phase A and 100% acetonitrile as mobile phase B, the concentration of bedaquiline is determined using a pre-plotted calibration curve.EFFECT: determination of bedaquiline in human blood plasma in a time not exceeding 6 minutes.1 cl, 9 dwg, 6 tbl

There is an urgent need for an effective therapeutic vaccine against tuberculosis (TB), which remains a major public health problem. Current "classical" strategies under development have failed or are suboptimal, and more effective vaccines are needed to achieve the World Health Organization's 2035 End TB Strategy. We have generated a post-exposure / therapeutic TB vaccine candidate (CD40.TB) whose heavy chain consists of an antibody directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells) conjugated to three relevant Mycobacterium tuberculosis (Mtb) antigens and which is liable to induce potent anti-TB humoral and cellular immunity.

The invention relates to the field of vaccines, in particular to application of a bacillus calmette-guerin vaccine and a complete freund's adjuvant in preparation of tuberculosis prevention vaccines. The invention provides a novel inoculation strategy of subcutaneous combined inoculation of the bacillus calmette guerin vaccine and the complete freund's adjuvant, the safety consistent with that of the existing tuberculosis prevention vaccine in the clinical stage is achieved, and the immune protection effect higher than that of the existing tuberculosis prevention vaccine in the clinical stage and the preclinical research stage is achieved. The compound is expected to be used as a novel tuberculosis vaccine for preventing tuberculosis.

The invention discloses a nanometer antibody of mycobacterium tuberculosis early secretory protein ESAT-6 and application thereof, relates to the technical field of antibody recombination and genetic engineering antibodies, and is characterized by providing two nanometer antibodies AEN1 and AEN5 which are derived from a total synthesis alpaca nanometer antibody yeast display library and are combined with ESAT-6 in high affinity, DNA sequences for coding the AEN1 and the AEN5, a carrier containing the DNA, a carrier containing the carrier containing the DNA, and a carrier containing the carrier containing the carrier containing the DNA. The invention relates to a vector, a host cell containing the vector, and a method for preparing AEN1 and AEN5 by utilizing genetic engineering. And the method for quantitatively detecting the ESAT-6 by using the double-antibody sandwich ELISA is established. Detection on clinical specimens of tuberculosis shows that the sensitivity of the diagnosis method is 94.9%, and the specificity is 100%. The antibody is used for preparing gold-labeled rapid test paper, and the ESAT-6 can be rapidly detected from serum of a mycobacterium tuberculosis infected patient.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting BCG (bacillus calmette guerin) BCG3965 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 3-5; and the light chain variable region CDR sequences are as shown in SEQ ID NO: 7-9. The monoclonal antibody 5F10 shows efficient antituberculous activity in vivo and in vitro through specific targeting of BCG3965 protein on the surface of mycobacterium tuberculosis, mainly including the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 5F10 is clear in sequence and structure, easy to develop and modify, and capable of being used for preparing antituberculous drugs for treating mycobacterium tuberculosis. The monoclonal antibody 5F10 disclosed by the invention has the advantages that the monoclonal antibody 5F10 is not easy to induce pathogens to generate drug resistance by an immune-mediated treatment mechanism, and the monoclonal antibody 5F10 is applied to prevention and treatment of tuberculosis, not only provides a new choice for treatment of tuberculosis, but also provides an important technical basis for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and is wide in application prospect.