304 results about "Tuberculosis mycobacterium" 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 present invention relates to a recombinant Mycobacterium bovis BCG strain comprising a plasmid having a short guide RNA (sgRNA) target sequence for knocking out the Mb3739 gene. Also provided are vaccine compositions for eliciting an immune response against Mycobacterium tuberculosis comprising a recombinant Mycobacterium bovis BCG strain engineered to activate the NOD-1 pathway. The recombinant Mycobacterium bovis BCG strain or vaccine composition can be used in a method against an immune response initiated by Mycobacterium tuberculosis. The invention also relates to a method for obtaining the recombinant bovine mycobacterium BCG strain.

The invention provides a compound as shown in a formula (I), a stereoisomer thereof, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a crystal form thereof, an isotope derivative thereof, a prodrug thereof and a metabolite thereof. The solvate or hydrate of the compound can be used for preparing a pharmaceutical composition for treating and / or preventing diseases related to mycobacterium tuberculosis and / or nontuberculous mycobacterium. The compound provided by the invention has an excellent bactericidal effect and strong specificity, has no cross resistance with the existing antituberculosis drugs, and provides a breakthrough direction for treatment of drug-resistant tuberculosis.

The invention discloses a combination of blocking agents for detecting drug resistance of mycobacterium tuberculosis. The combination comprises a first peptide nucleic acid blocking agent, a second peptide nucleic acid blocking agent, a third peptide nucleic acid blocking agent and a fourth peptide nucleic acid blocking agent. The first peptide nucleic acid blocker covers codons 511 and 513 of the rpoB gene. The second peptide nucleic acid blocker covers the codon 516 of the rpoB gene. And the third peptide nucleic acid blocking agent covers the codon 526 of the rpoB gene. And the fourth peptide nucleic acid blocking agent covers codons 531 and 533 of the rpoB gene. The respective sequences of the first peptide nucleic acid blocker, the second peptide nucleic acid blocker, the third peptide nucleic acid blocker, and the fourth peptide nucleic acid blocker match the wild type of the corresponding sequence of the rpoB gene. The invention also provides a kit and a method for detecting the drug resistance of mycobacterium 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.

This invention provides a data storage method and system for tuberculosis detection, relating to the field of tuberculosis detection technology. The data storage method for tuberculosis detection includes the following steps: S1. Collecting whole-genome sequencing data of Mycobacterium tuberculosis, host serum IgG titer, and drug sensitivity test results; S2. Calculating genetic distance D based on a reverse evolution model to generate four-dimensional spatiotemporal coordinates (t, x, y); S3. Performing data partitioning and storage based on the drug target barrier value β; S4. Generating dynamic metadata using a host-pathogen dynamics model and compressing and storing it. This invention implements a dynamic storage entropy adjustment algorithm at the hardware and software collaborative level, continuously optimizing the matching efficiency of data compression and physical storage. This results in an intelligent data hub that can perceive the evolutionary pulse of pathogens and autonomously optimize resources, providing support for clinical tuberculosis prevention and control decisions with temporal depth, spatial correlation, and risk evolution.

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.

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 CRISPR-Cas13a (clustered regularly interspaced short palindromic repeats-CRISPR-Cas13a) double crRNA (ribonucleic acid) system which is established by using ERASE test paper and is used for detecting the rifampicin resistance of mycobacterium tuberculosis on site. The CRISPR-Cas13a double crRNA-system comprises a Cas13a protein and crRNA, or a complex formed by the Cas13a protein and the crRNA; the crRNA comprises an anchoring sequence and a guide sequence; the anchoring sequence is used for being combined with Cas13a protein; the guide sequence is used for targeting mutation target sequences of sites 531, 526, 516 and 513 in a mycobacterium tuberculosis drug-resistant gene rpoB gene; the target sequence of the mycobacterium tuberculosis is located at the 2317th site to the 2597th site of the rifampicin drug-resistant gene rpoB. On the basis of a CRSPR-Cas13a nucleic acid detection technology, result interpretation is performed through RAA amplification in combination with a line elimination method (ERASE) lateral flow chromatography test paper, and experiments prove that the kit can target high-frequency mutation sites of four rifampicin drug-resistant genotypes at the same time, has good detection sensitivity and specificity, and can be used for detecting the rifampicin drug-resistant genotypes of the rifampicin drug-resistant genotypes of the rifampicin drug-resistant genotypes of the rifampicin drug-resistant genotypes. The method can realize rapid, efficient, simple and convenient detection of mycobacterium tuberculosis rifampicin drug-resistant nucleic acid, has a sensitivity of 10 copies / [mu] L, and has an important application value.

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.

The invention is applicable to the field of genetic engineering, and provides a mycobacterium tuberculosis Mce1A-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis Mce1A-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis Mce1A protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis Mce1A-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. The Mce1A-LS protein nanoparticle provided by the invention is high in immunogenicity, the protein Mce1A with high immunogenicity can induce to generate a synergistic immune effect and is high in safety, and the expressed fusion protein is non-toxic and harmless, so that the biosafety is high, in addition, the immune effect of the Mce1A-LS protein nanoparticle is good, and after the Mce1A-LS protein nanoparticle is used for immunizing a mouse, the immunogenicity of the Mce1A-LS protein nanoparticle is greatly improved. Strong body fluid and / or cellular immune response can be generated, which indicates that after immunization, a specific immune effect can be generated in a mouse body.

The application belongs to the technical field of biological medicine, and particularly relates to a blood Mycobacterium tuberculosis complex free nucleic acid detection kit and a detection method. The application first proposes a kit, wherein a PCR detection reagent group and a CRISPR / Cas12a detection reagent group are arranged in the kit; the PCR detection reagent group comprises a forward primer and a reverse primer which target a complex target; the sequence of the forward primer is overlapped with or complementary to the recognition region of the crRNA sequence, or the sequence of the reverse primer is overlapped with or complementary to the recognition region of the crRNA sequence.

The invention discloses a detection system and method for identifying mycobacteria and drug resistance genes of the mycobacteria based on nanopore sequencing, and relates to the field of biological medicine, the detection system comprises a specific targeted enrichment module, a nanopore sequencing module and a biological information analysis module; the specific targeted enrichment module comprises a probe combination, and the probe combination covers a mycobacterium tuberculosis complex conservative identification gene, species-specific genes of common nontuberculous mycobacteria and mycobacterium leprosy, and full-length or partial sequences of drug resistance related genes in a targeted manner; by utilizing the characteristics of nanopore length reading length and real-time sequencing and a tuberculosis specific targeted enrichment strategy, accurate identification of a mycobacterium tuberculosis complex group, synchronous typing of 42 mycobacteria, analysis of 24 drug-resistant genes, and efficient detection of structural variation and low-abundance heterogeneity drug-resistant mutation are realized, the detection period is shortened, the detection cost is reduced, and the detection efficiency is improved. And a comprehensive and reliable technical basis is provided for accurate diagnosis and treatment of mycobacterium infection.

The application relates to a mycobacterium tuberculosis drug resistance phenotype prediction method and device and a computer device. The method comprises the following steps: determining a to-be-predicted mutation site which does not exist in a mutation phenotype annotation database from at least one mutation site of a target gene fragment of to-be-processed mycobacterium tuberculosis according to gene sequencing data of the mycobacterium tuberculosis; converting protein structure change data of the to-be-predicted mutation site according to protein structure data corresponding to the to-be-predicted mutation site; inputting the protein structure change data of the to-be-predicted mutation site into a drug resistance phenotype prediction model to obtain a predicted drug resistance phenotype of the to-be-predicted mutation site; and determining a drug resistance phenotype prediction result of the to-be-processed mycobacterium tuberculosis based on the predicted drug resistance phenotype of the to-be-predicted mutation site and drug resistance phenotypes of the mutation sites except the to-be-predicted mutation site. The method can effectively improve the mycobacterium tuberculosis drug resistance phenotype prediction efficiency.

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.

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.

Provided are a Mycobacterium sp., a method for isolating same, and use thereof. The preservation number of the Mycobacterium sp. is CGMCC No. 21272 or CGMCC No. 21273. The Mycobacteria sp. has significant nitrogen fixation, carbon fixation, and ammonia oxidation capacity, can directly oxidize ammonia nitrogen into nitrogen, and has an antagonistic effect on other microorganisms.

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.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting mycobacterium tuberculosis MPT83 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: 5-7; cDR sequences of a light chain variable region are as follows: SEQ ID NO: 9-10 and LAS. The monoclonal antibody 9C9 can be specifically combined with MPT83 protein on the surface of Mycobacterium tuberculosis (MTB) and shows efficient antituberculous activity in vivo and in vitro, the activity mainly comprises 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 9C9 is clear in sequence and structure, easy to develop and modify and capable of being used for preparing the anti-tubercle bacillus monoclonal antibody 9C9. The monoclonal antibody 9C9 disclosed by the invention has the advantages that the monoclonal antibody 9C9 can be used for preventing and treating tuberculosis, an immune-mediated treatment mechanism of the monoclonal antibody 9C9 does not easily induce pathogens to generate drug resistance, a new choice is provided for the treatment of tuberculosis when the monoclonal antibody 9C9 is applied to prevention and treatment of tuberculosis, an important technical basis is also provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The invention provides a composition (e.g., pharmaceutical composition) comprising a combination of two or more phages, wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The invention provides a method of treating, reducing, or preventing a disease caused by Mycobacterium tuberculosis in a mammal comprising administering a pharmaceutical composition comprising a combination of two or more phages wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The composition can be administered alone or in combination with one or more antibiotics, wherein the length of treatment is reduced as compared to the length of treatment with one or more antibiotics alone.

The application discloses a kind of non-tuberculous mycobacterial lung disease and pulmonary tuberculosis CT image classification method, mainly including the following steps: image feature map is extracted by encoder and image feature map is divided into multiple examples, each example represents the feature information in certain area of image;The correlation weight of example and classification task is calculated, and the example is aggregated into bag feature representation according to the weight to express the characteristics of CT image;Bag feature representation is predicted as CT image category by classifier;According to the correlation weight, important examples are selected, and are evaluated by classifier, to express the correlation degree of the learning content and expected content of network;Loss function is constructed, including bag classification loss and correlation loss, respectively representing the difference between CT predicted value and true value and the difference between model learning content and expected content.The method can realize the binary classification of non-tuberculous mycobacterial lung disease and pulmonary tuberculosis CT image, and is superior to the classification accuracy of existing method.

The present invention is directed to a vaccine composition against a disease caused by Mycobacterium tuberculosis, said composition comprising at least four nucleic acids selected from the following groups: a. a nucleic acid encoding an Ag85A, Ag85B, or Ag85C antigen; b. a nucleic acid encoding a resuscitation promoting factor (Rpf) selected from the group consisting of: RpfA, RpfB, RpfC, RpfD and RpfE; c. a nucleic acid encoding a PE / PPE antigen selected from the group consisting of: PE5, PE13, PE15, PE29, PE31, PPE1, PPE2, PPE18, PPE20, and PPE68; d. a nucleic acid encoding a disease-reactivation-related antigen selected from the group consisting of: Rv1234 / MMAR_4207, and Rv0359 / MMAR_0678, wherein said vaccine composition comprises at least one nucleic acid from each of group a, b, and c; and wherein the nucleic acids are provided on one or more nucleic acids constructs.

The invention provides a mycobacterium tuberculosis attenuated live vaccine strain solid culture medium as well as preparation and application thereof, and the raw material of the solid culture medium comprises supernate obtained by filtering potato water prepared from selenium-enriched yellow-core potatoes with the total selenium content of 15-150mu g / kg. A solid culture medium without animal-derived components is obtained; and the culture method is further optimized, so that the mycobacterium tuberculosis is high in thallus proliferation speed and not easy to be infected by infectious microbes when being cultured. The solid culture medium disclosed by the invention is simple in manufacturing process, low in implementation cost and high in conversion efficiency, and has a prominent popularization prospect.

The application provides a primer probe set and a kit for detecting a rifampicin-resistant gene of Mycobacterium tuberculosis, and belongs to the technical field of molecular biology detection.The primer probe set comprises RAA primers and qPCR primers targeting the rpoB gene, probe primers targeting the wild-type rpoB gene, and probe primers targeting the mutant rpoB gene.The application adopts the detection methods of RT-RAA and qPCR in sequence, and the above specific primer probe set can be combined to simultaneously and rapidly detect the 516, 526, 531 and 533 sites of the rpoB gene of Mycobacterium tuberculosis, has good specificity, and the detection sensitivity can reach 5 copies / ul, is 20 times higher than the sensitivity of qPCR (100 copies / ul), and has a 5% detection capability for heterogenic drug resistance mutation; the detection method can also greatly shorten the detection time.

The invention belongs to the technical field of pathogen molecular diagnosis, and particularly relates to a mycobacterium tuberculosis detection primer group, method and kit based on multiple PCR (Polymerase Chain Reaction) and high-throughput sequencing. The primer combination aiming at a plurality of high-copy and single-copy gene areas of the mycobacterium tuberculosis is designed through a unique bioinformatics process, and the capturing capacity and amplification efficiency of a low-bacterium-amount sample are fundamentally improved. A pollution discrimination rule based on multi-target consistency verification is established by using NGS multi-target data features, so that pollution identification is internalized into a part of a data analysis process. According to the invention, the optimized mycobacterium tuberculosis specific primer group and the primer pool covering other common respiratory pathogens are integrated in the same multiplex PCR reaction system, so that synchronous and efficient detection of mycobacterium tuberculosis and other pathogens is realized, and the diagnosis efficiency and range are greatly improved.

This application relates to the field of biomedical technology, and in particular to the application of a small molecule D6 and its derivatives in the preparation of anti-tuberculosis drugs. Through research, this application has discovered that small molecule D6 can specifically target methionine synthase in Mycobacterium tuberculosis to block the methionine synthesis pathway, thereby causing metabolic disorders and cell death in the bacteria. Furthermore, this small molecule D6 exhibits significant antibacterial activity against various Mycobacterium tuberculosis strains, including drug-resistant and dormant strains. Therefore, this small molecule D6 can be well-suited for the preparation of anti-tuberculosis drugs.