181 results about "Tuberculosis mycobacterium" patented technology

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 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 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 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 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 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 biological medicines, and particularly relates to application of a compound NSC348884 in preparation of a medicine for resisting mycobacterium tuberculosis. Experimental results show that the NSC348884 has remarkable in-vitro bacteriostatic activity on standard strains and clinical isolates of mycobacterium tuberculosis. The MIC of the strain to a standard strain is 2 [mu] g / mL, and the MIC distribution of the strain to a clinical isolated strain is 0.5-4 [mu] g / mL. Further bacteriostatic activity evaluation shows that after the mycobacterium tuberculosis is treated by NSC348884 (1 [mu] g / mL) for 3 days, the growth of the mycobacterium tuberculosis is obviously inhibited, and the inhibition rate is 41.82% + / -10.14%. Compared with a DMSO control group, the CFU is reduced by about 0.24 log. The discovery prompts that NSC348884 has the potential of being developed into a novel anti-tuberculosis drug.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting Mycobacterium tuberculosis PspA and a preparation method and application thereof, the protective monoclonal antibody comprises at least one of the following CDR sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 4-6; the light chain variable region CDR sequences are as shown in SEQ ID NO: 8-9 and WAS. The antibody or the antigen binding fragment can specifically bind to PspA protein of mycobacterium tuberculosis (MTB), shows efficient antituberculous activity in vivo and in vitro, specifically, can significantly enhance phagocytosis of macrophages on tubercle bacillus, inhibit tubercle bacillus growth and the like, and is clear in sequence and structure, so that the antibody or the antigen binding fragment is easy to develop and transform, and has broad application prospects. And moreover, an immune-mediated treatment mechanism is not easy to induce pathogens to generate drug resistance, so that when being applied to prevention and treatment of tuberculosis, not only is a new choice provided for treatment of tuberculosis, but also an important basis is provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The application discloses a pyridine derivative, an intermediate, a preparation method and application. Specifically disclosed is a compound as shown in formula I or a pharmaceutically acceptable salt thereof. The pyridine derivative of the application can inhibit the growth of sensitive Mycobacterium tuberculosis, drug-resistant Mycobacterium tuberculosis, and in particular, bedaquiline drug-resistant strains, and has the advantages of longer elimination half-life in pharmacokinetics and higher safety.

This invention relates to the field of pharmaceutical application technology, and more specifically, to the application of heterocyclic compounds. Example I describes the application of the compound shown in Formula I in the preparation of an inhibitor that inhibits the activity of methylenetetrahydrofolate reductase. Furthermore, the compound shown in Formula I can be used alone, in combination with para-aminosalicylic acid, or in combination with a β-lactamase inhibitor, all of which exhibit good antibacterial activity against Mycobacterium tuberculosis, and can treat or prevent diseases caused by Mycobacterium tuberculosis, such as tuberculosis.

The present application relates to a method for increasing the adhesion of a slide, belonging to the technical field of biological medicine, to solve at least one of the problems in the prior art, such as poor adhesion of mycobacterium tuberculosis on the slide, easy to drop the slide in subsequent operation, serious loss of mycobacterium tuberculosis, and influence on the diagnosis rate of pulmonary tuberculosis. The dextromethorphan hydrobromide tablets and the flaxseed gum can generate a high molecular water-soluble polymer with strong positive charge adhesion under the action of a catalyst, that is, the binder described in the present application. Since mycobacterium tuberculosis is the pathogen causing tuberculosis, its surface has a large number of negative charges. Once the mycobacterium tuberculosis with negative charges on the surface contacts the binder containing a large number of positive charges, the surface of the mycobacterium tuberculosis will be quickly wrapped by the binder, forming a firm adhesion layer, and the problem of easy dropping of the slide will not occur during staining and subsequent detection.

The invention discloses a mycobacterium tuberculosis mRNA (messenger Ribonucleic Acid) vaccine as well as a construction method and application thereof, and belongs to the technical field of biological medicines. The technical problem to be solved is to provide a novel mycobacterium tuberculosis mRNA vaccine which is low in dosage, high in safety and lasting in immune memory. According to the technical scheme, the preparation method is characterized by comprising the following steps: carrying out tandem expression on antigens for coding Hsp65 and Mpt83, constructing mRNA molecules by combining tPA signal peptide (SEQ ID NO: 1), an MITD sequence (SEQ ID NO: 5) and flexible Linker (SEQ ID NO: 6-7), and carrying out codon optimization (an mRNA secondary structure and GC content) and a lipid nanoparticle (LNP) encapsulation process to finally obtain the novel mycobacterium tuberculosis mRNA vaccine.

The present invention relates to polygenic nucleic acid constructs comprising nucleotide sequences encoding Mycobacterium tuberculosis antigens and to mRNA vaccine constructs transcribed or obtained therefrom. Also provided are lipid nanoparticles including the mRNA vaccine constructs and vaccine compositions comprising the constructs described. The constructs, lipid nanoparticles containing them, and vaccine compositions described may be useful in methods for eliciting a protective immune response against Mycobacterium tuberculosis in a subject.

The present disclosure discloses a method for efficient catalytic synthesis of PAPS based on constructing an ATP regeneration system, and belongs to the technical field of bioengineering. Efficient production of PAPS is realized through microbial recombination expression and artificial construction of PAPS bifunctional synthetase. On the basis, an ATP regeneration system coupling with polyphosphate kinase from Corynebacterium glutamicum and Mycobacterium tuberculosis can be used for recovering two byproducts: pyrophosphoric acid and ADP at the same time, the equivalent conversion of a substrate and a product is realized, the PAPS generated in a catalysis system has high purity, and the sulfonic acid group donation in most sulfonic acid transfer reactions can be realized.

The invention is applicable to the field of gene engineering, and provides a mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle, a preparation method and application thereof, the mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle is formed by sequence fusion of mycobacterium tuberculosis Ag85B protein, TB8.4 protein and LS protein, and the amino acid sequence of the mycobacterium tuberculosis Ag85B-TB8.4-LS protein nanoparticle is shown as SEQ ID NO: 2 in a sequence table. According to the invention, by virtue of a gene recombination technology, key immunogens Ag85B and TB8.4 of mycobacterium tuberculosis are combined with an LS protein fusion vector, and the Ag85B-TB8.4-LS protein nanoparticles with uniform particle size and stable structure are efficiently produced by virtue of an escherichia coli expression system. Animal experiment results show that the Ag85B-TB8.4-LS protein nanoparticle can simultaneously excite strong humoral immunity and cellular immunity response, not only brings a new idea for research and development of tuberculosis vaccines, but also can be popularized and applied to research and development of other infectious disease vaccines due to the modular design, and has important scientific significance and industrialization prospects.

The present invention relates to pyridine-2-thiol 1-oxide derivatives and their use as antimicrobial agents in infectious diseases of mammals (humans and animals) caused by fungi or bacteria, in particular belonging to the Mycobacteriaceae family, especially diseases caused by Mycobacterium abscessus or Mycobacterium tuberculosis.

The invention relates to the technical fields of medicines and luminescent materials. The invention discloses a 1, 6-naphthyridine amine compound as shown in a formula (I), a preparation method thereof, a pharmaceutical composition taking the compound as an active ingredient, application of the 1, 6-naphthyridine amine compound in preparation of a medicine for treating cancer, application of the 1, 6-naphthyridine amine compound in preparation of a medicine for treating and / or preventing infectious diseases caused by mycobacterium tuberculosis and application of the 1, 6-naphthyridine amine compound in preparation of a fluorescent dye. Wherein R1, R2, R3 and A ring are described in the specification.

In one aspect, the disclosure relates to compounds effective in the treatment of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis as well as drug-sensitive tuberculosis, methods of making the same, pharmaceutical compositions comprising the same, and methods of treating bacterial infections caused by Mycobacterium tuberculosis using the same. In an aspect, the compounds and pharmaceutical compositions are not cytotoxic. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

The present invention relates to a Mycobacterium tuberculosis vaccine. Specifically, the vaccine comprises an immune composition, and the immune composition comprises an antigen component and a particle protein component. The particle protein component comprises a nanoparticle protein, and the antigen component and the particle protein component are covalently combined by means of a binding peptide 1 and a binding peptide 2 to form an immunogenic complex. The vaccine can induce or stimulate humoral and cellular immune responses. Also disclosed is a preparation method for the Mycobacterium tuberculosis vaccine. The method is simple, cost-effective, and suitable for large-scale production.