332 results about "Mycobacterium" patented technology

The invention discloses two mycobacterium bacteriophages and application thereof. The two bacteriophages both have a splitting spectrum width and efficient splitting capability, can specifically realize effective splitting of mycobacteria of five specific sequence types, and are further applied to the field of prevention and control of mycobacteria. Specifically, the bacteriophage MP2435 and the bacteriophage MP2451 not only can effectively inhibit the proliferation process of mycobacteria and block the formation of a biofilm of the mycobacteria, but also can efficiently kill the mycobacteria in a milk matrix; meanwhile, the two bacteriophages can still keep relatively high activity under the conditions that the temperature is 37-65 DEG C and the pH value is 3-12, and the bactericidal activity of the bacteriophages can be stably maintained even in acid-base, high-temperature and ultraviolet-containing extreme environments. Through the characteristics, the application scene and application range of the bacteriophage in mycobacterium prevention and control are remarkably widened, and an efficient and stable novel technical means is provided for biological prevention and control of mycobacterium.

The invention relates to the technical field of gene detection, and discloses a mycobacterium tuberculosis drug resistance gene detection data analysis system which comprises a data import module, a signal correction module, a feature extraction module, a multi-stage interpretation module, a result fusion module and a report generation module. The system performs baseline drift correction, abnormal point detection and nonlinear normalization on a fluorescence intensity value output by a detector, extracts multi-dimensional features such as peak intensity, a mutation ratio, a consistency coefficient and an in-batch difference index, and constructs a dynamic threshold function to realize wild type and mutation type layered judgment. A drug resistance risk conclusion is generated through drug resistance characteristic matrix mapping, a standardized detection report is output, and intelligent analysis of a detection result and automatic report generation are achieved. Through multi-stage signal correction, multi-dimensional feature extraction and dynamic threshold interpretation, intelligent analysis and standardized report output of a mycobacterium tuberculosis drug resistance gene detection result are realized, and data judgment accuracy and clinical application efficiency are improved.

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 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 discloses a method for establishing indirect ELISA (enzyme-linked immunosorbent assay) for detecting mycobacterium bovis Lprl, which comprises the following steps: preparing mycobacterium bovis Lprl protein, taking the purified protein as an antigen, and determining conditions such as optimal antigen coating concentration, serum dilution, serum incubation time, secondary antibody dilution concentration, incubation time and the like. The established indirect ELISA detection method does not have cross reaction with other bovine pathogens, the specificity is good, the detection accuracy is high, and the total coincidence rate of test results of intradermal allergy with bovine tubercle bacillus is 95.8%; the intra-batch variation coefficient of the detected samples is 2.43%-3.61%, the inter-batch variation coefficient is 2.83%-3.96%, and the intra-batch variation coefficient and the inter-batch variation coefficient are both smaller than 10%. A new diagnosis target is developed, the established indirect ELISA method has the characteristics of high sensitivity, strong specificity, good repeatability and the like, the operation is easy, and a new method is provided for the detection work of the mycobacterium bovis.

The present invention provides a bacteriophage having a bacteriolytic activity against Mycobacterium avium and / or Mycobacterium intracellularis, the bacteriophage having a genome containing a nucleic acid sequence represented by the genome of the bacteriophage specified by the preservation number NITE BP-03513 or NITE BP-03514 or the preservation number NITE BP-03918, the bacteriophage having a bacteriolytic activity against Mycobacterium avium and / or Mycobacterium intracellularis, and the bacteriophage having a bacteriolytic activity against Mycobacterium avium and / or Mycobacterium intracellularis. The capsid of the phage is connected with the cell-penetrating peptide through a tag.

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 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.

To provide methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle.SOLUTION: The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The method provided herein results in a change from the baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and / or NTM culture conversion to negative during or after the administration period.SELECTED DRAWING: None

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 present disclosure relates to micellar compositions conformed by biomimetic phospholipids and nonionic surfactants, among other ingredients, for eliminating one or more types of microorganisms including mycobacteria, bacteria, fungi, and viruses from a surface within a contact time on the surface of less than about 1 minutes and having pH of from about 0.3 to 8. The present invention aims on using 100% bio-based (renewable) biodegradable, non-toxic ingredients to be applied not only to hard inanimate surfaces but also on tissue for endodontic applications.

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 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 an organic boron compound of formula I or a salt thereof, a pharmaceutical composition thereof, and uses of the organic boron compound and the pharmaceutical composition in the treatment of non-tuberculous mycobacterial infections. [Chemical 1] TIFF2025520237000027.tif49159

The invention discloses a detection kit based on orthogonal dual-channel label-free CRISPR-Cas and application of the detection kit, relates to the technical field of nucleic acid detection, and constructs an orthogonal dual-channel response system by utilizing the differentiated cleavage activity of Cas12a targeted DNA and Cas13 targeted RNA to a substrate. A Cas12a pathway is reported by utilizing protoporphyrin IX to be compounded with G-quadruplex G4DNA, and a Cas13a pathway is reported by utilizing DFHBI to be compounded with a Broccoli RNA structure, so that label-free signal transduction is realized. Through accurate screening of fluorophores, channel specificity is ensured, and optical signal crosstalk is eliminated. Mycobacterium tuberculosis (MTB) and respiratory syncytial virus (RSV) are used as model pathogens for verification, and a multiple recombinase polymerase amplification (RPA) technology is combined, so that the detection sensitivity on a synthetic target reaches a single molecule level. The system has high specificity, and even if the concentration of a non-target pathogen is increased by 100 times, no cross reaction exists.

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.

To provide monoclonal antibodies specific to epitopes found within lipoarabinomannan (LAM) and phosphatidyl-myo-inositol mannoside 6 (PIM6) for the diagnosis and treatment of Mycobacterium tuberculosis infections.SOLUTION: The present invention provides a monoclonal anti-PIM6 / LAM antibody, or an antigen-binding portion thereof, that specifically binds to an epitope present in LAM and PIM6, the epitope including at least one polymannose structure. The anti-PIM6 / LAM antibody includes CDR1 light chain variable region, CDR2 light chain variable region, CDR3 light chain variable region, CDR1 heavy chain variable region, CDR2 heavy chain variable region, and CDR3 heavy chain variable region, each including a specific amino acid sequence.SELECTED DRAWING: Figure 1

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 provides methods and compositions for modulating the immune system of an individual. The methods provided herein entail administering a composition comprising a killed or inactivated Mycobacterium or antigenic fragments derived therefrom. Also provided herein are methods for assessing alteration of immune system functioning following administration of a composition comprising aa killed or inactivated Mycobacterium or antigenic fragments derived therefrom.