Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.Tuberculosis: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts.Tuberculosis, Pulmonary: MYCOBACTERIUM infections of the lung.Mycobacterium bovis: The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.Mycobacterium smegmatis: A rapid-growing, nonphotochromogenic species of MYCOBACTERIUM originally isolated from human smegma and found also in soil and water. (From Dorland, 28th ed)Mycobacterium Infections: Infections with bacteria of the genus MYCOBACTERIUM.Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.Tuberculosis, Multidrug-Resistant: Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.Nontuberculous Mycobacteria: So-called atypical species of the genus MYCOBACTERIUM that do not cause tuberculosis. They are also called tuberculoid bacilli, i.e.: M. buruli, M. chelonae, M. duvalii, M. flavescens, M. fortuitum, M. gilvum, M. gordonae, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. kansasii, M. marinum, M. obuense, M. scrofulaceum, M. szulgai, M. terrae, M. ulcerans, M. xenopi.Bacterial Proteins: Proteins found in any species of bacterium.Tuberculosis Vaccines: Vaccines or candidate vaccines used to prevent or treat TUBERCULOSIS.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Mycobacterium leprae: A species of gram-positive, aerobic bacteria that causes LEPROSY in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side.Mycobacterium avium Complex: A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS; M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs.Mycobacterium Infections, Nontuberculous: Infections with nontuberculous mycobacteria (atypical mycobacteria): M. kansasii, M. marinum, M. scrofulaceum, M. flavescens, M. gordonae, M. obuense, M. gilvum, M. duvali, M. szulgai, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. xenopi (littorale), M. ulcerans, M. buruli, M. terrae, M. fortuitum (minetti, giae), M. chelonae.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.BCG Vaccine: An active immunizing agent and a viable avirulent attenuated strain of Mycobacterium tuberculosis, var. bovis, which confers immunity to mycobacterial infections. It is used also in immunotherapy of neoplasms due to its stimulation of antibodies and non-specific immunity.Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Antibiotics, Antitubercular: Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.Sputum: Material coughed up from the lungs and expectorated via the mouth. It contains MUCUS, cellular debris, and microorganisms. It may also contain blood or pus.Mycobacterium marinum: A moderate-growing, photochromogenic species found in aquariums, diseased fish, and swimming pools. It is the cause of cutaneous lesions and granulomas (swimming pool granuloma) in humans. (Dorland, 28th ed)Mycobacterium fortuitum: A rapid-growing, nonphotochromogenic species that is potentially pathogenic, producing lesions of lung, bone, or soft tissue following trauma. It has been found in soil and in injection sites of humans, cattle, and cold-blooded animals. (Dorland, 28th ed)Mycolic AcidsTuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection.Mycobacterium kansasii: A slow-growing, photochromogenic species that is the etiologic agent of a tuberculosis-like disease in humans and is frequently isolated from human pulmonary secretions or tubercles. The incidence of infection is sharply increased among immunocompromised individuals. (Dorland, 28th ed)Mycobacterium chelonae: A species of gram-positive, aerobic bacteria commonly found in soil and occasionally isolated from sputum. It causes postoperative wound infections as well as gluteal abscesses.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Tuberculosis, Bovine: An infection of cattle caused by MYCOBACTERIUM BOVIS. It is transmissible to man and other animals.Bacteriological Techniques: Techniques used in studying bacteria.Tuberculosis, Miliary: An acute form of TUBERCULOSIS in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the blood stream.Mycobacteriophages: Viruses whose host is one or more Mycobacterium species. They include both temperate and virulent types.Latent Tuberculosis: The dormant form of TUBERCULOSIS where the person shows no obvious symptoms and no sign of the causative agent (Mycobacterium tuberculosis) in the SPUTUM despite being positive for tuberculosis infection skin test.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Tuberculosis, Lymph Node: Infection of the lymph nodes by tuberculosis. Tuberculous infection of the cervical lymph nodes is scrofula.Mycobacterium avium subsp. paratuberculosis: A subspecies of gram-positive, aerobic bacteria. It is the etiologic agent of Johne's disease (PARATUBERCULOSIS), a chronic GASTROENTERITIS in RUMINANTS.Mycobacterium avium-intracellulare Infection: A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.DNA Fingerprinting: A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.Tuberculosis, Meningeal: A form of bacterial meningitis caused by MYCOBACTERIUM TUBERCULOSIS or rarely MYCOBACTERIUM BOVIS. The organism seeds the meninges and forms microtuberculomas which subsequently rupture. The clinical course tends to be subacute, with progressions occurring over a period of several days or longer. Headache and meningeal irritation may be followed by SEIZURES, cranial neuropathies, focal neurologic deficits, somnolence, and eventually COMA. The illness may occur in immunocompetent individuals or as an OPPORTUNISTIC INFECTION in the ACQUIRED IMMUNODEFICIENCY SYNDROME and other immunodeficiency syndromes. (From Adams et al., Principles of Neurology, 6th ed, pp717-9)Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Tuberculosis, Cutaneous: Tuberculosis of the skin. It includes scrofuloderma and tuberculid, but not LUPUS VULGARIS.Bacterial Typing Techniques: Procedures for identifying types and strains of bacteria. The most frequently employed typing systems are BACTERIOPHAGE TYPING and SEROTYPING as well as bacteriocin typing and biotyping.Mycobacterium phlei: A saprophytic bacterium widely distributed in soil and dust and on plants.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Extensively Drug-Resistant Tuberculosis: Tuberculosis resistant to ISONIAZID and RIFAMPIN and at least three of the six main classes of second-line drugs (AMINOGLYCOSIDES; polypeptide agents; FLUOROQUINOLONES; THIOAMIDES; CYCLOSERINE; and PARA-AMINOSALICYLIC ACID) as defined by the CDC.Mycobacterium ulcerans: A slow-growing mycobacterium that infects the skin and subcutaneous tissues, giving rise to indolent BURULI ULCER.Tuberculosis, Osteoarticular: Tuberculosis of the bones or joints.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Tuberculosis, Pleural: Tuberculosis of the serous membrane lining the thoracic cavity and surrounding the lungs.Tuberculin: A protein extracted from boiled culture of tubercle bacilli (MYCOBACTERIUM TUBERCULOSIS). It is used in the tuberculin skin test (TUBERCULIN TEST) for the diagnosis of tuberculosis infection in asymptomatic persons.Tuberculosis, Gastrointestinal: TUBERCULOSIS that involves any region of the GASTROINTESTINAL TRACT, mostly in the distal ILEUM and the CECUM. In most cases, MYCOBACTERIUM TUBERCULOSIS is the pathogen. Clinical features include ABDOMINAL PAIN; FEVER; and palpable mass in the ileocecal area.DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Tuberculosis, Spinal: Osteitis or caries of the vertebrae, usually occurring as a complication of tuberculosis of the lungs.Genes, Bacterial: The functional hereditary units of BACTERIA.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Ethionamide: A second-line antitubercular agent that inhibits mycolic acid synthesis.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.Capreomycin: Cyclic peptide antibiotic similar to VIOMYCIN. It is produced by Streptomyces capreolus.Cord Factors: Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals.Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Minisatellite Repeats: Tandem arrays of moderately repetitive, short (10-60 bases) DNA sequences which are found dispersed throughout the GENOME, at the ends of chromosomes (TELOMERES), and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit.Tuberculosis, Splenic: Infection of the spleen with species of MYCOBACTERIUM.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Genome, Bacterial: The genetic complement of a BACTERIA as represented in its DNA.Colony Count, Microbial: Enumeration by direct count of viable, isolated bacterial, archaeal, or fungal CELLS or SPORES capable of growth on solid CULTURE MEDIA. The method is used routinely by environmental microbiologists for quantifying organisms in AIR; FOOD; and WATER; by clinicians for measuring patients' microbial load; and in antimicrobial drug testing.Tuberculosis, Central Nervous System: Tuberculosis of the brain, spinal cord, or meninges (TUBERCULOSIS, MENINGEAL), most often caused by MYCOBACTERIUM TUBERCULOSIS and rarely by MYCOBACTERIUM BOVIS. The infection may be limited to the nervous system or coexist in other organs (e.g., TUBERCULOSIS, PULMONARY). The organism tends to seed the meninges causing a diffuse meningitis and leads to the formation of TUBERCULOMA, which may occur within the brain, spinal cord, or perimeningeal spaces. Tuberculous involvement of the vertebral column (TUBERCULOSIS, SPINAL) may result in nerve root or spinal cord compression. (From Adams et al., Principles of Neurology, 6th ed, pp717-20)Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Reagent Kits, Diagnostic: Commercially prepared reagent sets, with accessory devices, containing all of the major components and literature necessary to perform one or more designated diagnostic tests or procedures. They may be for laboratory or personal use.Molecular Epidemiology: The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Mycobacterium scrofulaceum: A non-tuberculous mycobacterium causing cervical lymphadenitis in children. It very rarely causes pulmonary disease, and is believed to be non-pathogenic in animals.Tuberculosis, Urogenital: A general term for MYCOBACTERIUM infections of any part of the UROGENITAL SYSTEM in either the male or the female.Phagosomes: Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.Tuberculosis, Ocular: Tuberculous infection of the eye, primarily the iris, ciliary body, and choroid.Mice, Inbred C57BLLeprosy: A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid.Tuberculosis, Hepatic: Infection of the LIVER with species of MYCOBACTERIUM, most often MYCOBACTERIUM TUBERCULOSIS. It is characterized by localized small tuberculous miliary lesions or tumor-like mass (TUBERCULOMA), and abnormalities in liver function tests.AIDS-Related Opportunistic Infections: Opportunistic infections found in patients who test positive for human immunodeficiency virus (HIV). The most common include PNEUMOCYSTIS PNEUMONIA, Kaposi's sarcoma, cryptosporidiosis, herpes simplex, toxoplasmosis, cryptococcosis, and infections with Mycobacterium avium complex, Microsporidium, and Cytomegalovirus.Bacterial Load: Measurable quantity of bacteria in an object, organism, or organism compartment.Molecular Diagnostic Techniques: MOLECULAR BIOLOGY techniques used in the diagnosis of disease.Microbial Viability: Ability of a microbe to survive under given conditions. This can also be related to a colony's ability to replicate.Glycolipids: Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)Acyltransferases: Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Interspersed Repetitive Sequences: Copies of transposable elements interspersed throughout the genome, some of which are still active and often referred to as "jumping genes". There are two classes of interspersed repetitive elements. Class I elements (or RETROELEMENTS - such as retrotransposons, retroviruses, LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS) transpose via reverse transcription of an RNA intermediate. Class II elements (or DNA TRANSPOSABLE ELEMENTS - such as transposons, Tn elements, insertion sequence elements and mobile gene cassettes of bacterial integrons) transpose directly from one site in the DNA to another.Mycobacterium xenopi: A slow-growing, scotochromogenic species occurring usually harmlessly in human secretions but occasionally associated with chronic pulmonary disease. (Dorland, 28th ed)Mycobacterium lepraemurium: The etiologic agent of rat leprosy, also known as murine leprosy.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Chaperonin 60: A group I chaperonin protein that forms the barrel-like structure of the chaperonin complex. It is an oligomeric protein with a distinctive structure of fourteen subunits, arranged in two rings of seven subunits each. The protein was originally studied in BACTERIA where it is commonly referred to as GroEL protein.Evaluation Studies as Topic: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.Cell Wall: The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.Tuberculosis, Female Genital: MYCOBACTERIUM infections of the female reproductive tract (GENITALIA, FEMALE).Contact Tracing: Identification of those persons (or animals) who have had such an association with an infected person, animal, or contaminated environment as to have had the opportunity to acquire the infection. Contact tracing is a generally accepted method for the control of sexually transmitted diseases.Chaperonins: A family of multisubunit protein complexes that form into large cylindrical structures which bind to and encapsulate non-native proteins. Chaperonins utilize the energy of ATP hydrolysis to enhance the efficiency of PROTEIN FOLDING reactions and thereby help proteins reach their functional conformation. The family of chaperonins is split into GROUP I CHAPERONINS, and GROUP II CHAPERONINS, with each group having its own repertoire of protein subunits and subcellular preferences.Molecular Typing: Using MOLECULAR BIOLOGY techniques, such as DNA SEQUENCE ANALYSIS; PULSED-FIELD GEL ELECTROPHORESIS; and DNA FINGERPRINTING, to identify, classify, and compare organisms and their subtypes.RNA, Bacterial: Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.Paratuberculosis: A chronic GASTROENTERITIS in RUMINANTS caused by MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS.Mice, Inbred BALB CDNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Clofazimine: A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619)Directly Observed Therapy: A treatment method in which patients are under direct observation when they take their medication or receive their treatment. This method is designed to reduce the risk of treatment interruption and to ensure patient compliance.Nucleic Acid Amplification Techniques: Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template.South Africa: A republic in southern Africa, the southernmost part of Africa. It has three capitals: Pretoria (administrative), Cape Town (legislative), and Bloemfontein (judicial). Officially the Republic of South Africa since 1960, it was called the Union of South Africa 1910-1960.Tuberculosis, Renal: Infection of the KIDNEY with species of MYCOBACTERIUM.Rifamycins: A group of ANTI-BACTERIAL AGENTS characterized by a chromophoric naphthohydroquinone group spanned by an aliphatic bridge not previously found in other known ANTI-BACTERIAL AGENTS. They have been isolated from fermentation broths of Streptomyces mediterranei.Diarylquinolines: A class of quinoline compounds defined by the presence of two aromatic ring structures which are attached via a side chain to carbon 3 of the qunolinyl structure. The two aromatic moieties are typically NAPTHALENE and BENZENE. Several compounds in this class are used as ANTITUBERCULAR AGENTS.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.AmidohydrolasesTuberculosis, Endocrine: Infection of the ENDOCRINE GLANDS with species of MYCOBACTERIUM, most often MYCOBACTERIUM TUBERCULOSIS.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Aza CompoundsTuberculosis, Laryngeal: Tuberculosis involving the larynx, producing ulceration of the VOCAL CORDS and the LARYNGEAL MUCOSA.Spleen: An encapsulated lymphatic organ through which venous blood filters.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Truncated Hemoglobins: A family of hemoglobin-like proteins found in BACTERIA; PLANTS; and unicellular eukaryotes. Truncated hemoglobins are distantly related to vertebrate hemoglobins and are typically shorter than vertebrate hemoglobins by 20-40 residues.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Aminosalicylic Acid: An antitubercular agent often administered in association with ISONIAZID. The sodium salt of the drug is better tolerated than the free acid.PeroxidasesHIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Molecular Probe Techniques: The use of devices which use detector molecules to detect, investigate, or analyze other molecules, macromolecules, molecular aggregates, or organisms.Tuberculoma: A tumor-like mass resulting from the enlargement of a tuberculous lesion.RNA, Ribosomal, 16S: Constituent of 30S subunit prokaryotic ribosomes containing 1600 nucleotides and 21 proteins. 16S rRNA is involved in initiation of polypeptide synthesis.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Catalase: An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.Mycobacterium haemophilum: A species of gram-positive, aerobic bacteria that causes granulomatous or ulcerating skin lesions in immunosuppressed persons. This organism owes its name to its requirement for growth of high levels of iron, conveniently supplied as blood, heme, or ferric ammonium citrate.Coinfection: Simultaneous infection of a host organism by two or more pathogens. In virology, coinfection commonly refers to simultaneous infection of a single cell by two or more different viruses.Granuloma, Respiratory Tract: Granulomatous disorders affecting one or more sites in the respiratory tract.Colorimetry: Any technique by which an unknown color is evaluated in terms of standard colors. The technique may be visual, photoelectric, or indirect by means of spectrophotometry. It is used in chemistry and physics. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Armadillos: Burrowing, chiefly nocturnal mammals of the family Dasypodidae having bodies and heads encased in small bony plates. They are widely distributed in the warmer parts of the Americas.DNA Probes: Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.Host-Pathogen Interactions: The interactions between a host and a pathogen, usually resulting in disease.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Tuberculosis, Oral: Tuberculosis of the mouth, tongue, and salivary glands.Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Mycobacteriaceae: A family of gram-positive bacteria found in soil and dairy products and as parasites on animals and man. Several are important pathogens.Thioridazine: A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Specimen Handling: Procedures for collecting, preserving, and transporting of specimens sufficiently stable to provide accurate and precise results suitable for clinical interpretation.Toll-Like Receptor 2: A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.Thioacetazone: A thiosemicarbazone that is used in association with other antimycobacterial agents in the initial and continuation phases of antituberculosis regimens. Thiacetazone containing regimens are less effective than the short-course regimen recommended by the International Union Against Tuberculosis and are used in some developing countries to reduce drug costs. (From Martindale, The Extra Pharmacopoeia, 30th ed, p217)Nitrate Reductase: An enzyme that catalyzes the oxidation of nitrite to nitrate. It is a cytochrome protein that contains IRON and MOLYBDENUM.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures.Interferon-gamma Release Tests: The assay of INTERFERON-GAMMA released from lymphocytes after their exposure to a specific test antigen, to check for IMMUNOLOGIC MEMORY resulting from a previous exposure to the antigen. The amount of interferon-gamma released is usually assayed by an ENZYME-LINKED IMMUNOSORBENT ASSAY.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.Galactans: Polysaccharides composed of repeating galactose units. They can consist of branched or unbranched chains in any linkages.Peritonitis, Tuberculous: A form of PERITONITIS seen in patients with TUBERCULOSIS, characterized by lesion either as a miliary form or as a pelvic mass on the peritoneal surfaces. Most patients have ASCITES, abdominal swelling, ABDOMINAL PAIN, and other systemic symptoms such as FEVER; WEIGHT LOSS; and ANEMIA.Immunologic Tests: Immunologic techniques involved in diagnosis.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.Aerosols: Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Alanine Dehydrogenase: An NAD-dependent enzyme that catalyzes the reversible DEAMINATION of L-ALANINE to PYRUVATE and AMMONIA. The enzyme is needed for growth when ALANINE is the sole CARBON or NITROGEN source. It may also play a role in CELL WALL synthesis because L-ALANINE is an important constituent of the PEPTIDOGLYCAN layer.Emigration and Immigration: The process of leaving one's country to establish residence in a foreign country.IndiaQuinolinesProtein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Paleopathology: The study of disease in prehistoric times as revealed in bones, mummies, and archaeologic artifacts.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Radiography, Thoracic: X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Macrophages, Alveolar: Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Cell-mediated immunity: dealing a direct blow to pathogens. (1/9979)

Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis.  (+info)

Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis. (2/9979)

Mycobacterium tuberculosis attaches to, enters, and replicates within alveolar macrophages (AMs). Our previous studies suggest that surfactant protein A (SP-A) can act as a ligand in the attachment of M. tuberculosis to AMs. Reactive nitrogen intermediates (RNIs) play a significant role in the killing of mycobacteria. We have demonstrated that RNI levels generated by AMs were significantly increased when interferon-gamma-primed AMs were incubated with M. tuberculosis. However, the RNI levels were significantly suppressed in the presence of SP-A (10 microg/ml). The specificity of SP-A's effect was demonstrated by the use of F(ab')2 fragments of anti-SP-A monoclonal antibodies and by the use of mannosyl-BSA, which blocked the suppression of RNI levels by SP-A. Furthermore, incubation of deglycosylated SP-A with M. tuberculosis failed to suppress RNI by AMs, suggesting that the oligosaccharide component of SP-A, which binds to M. tuberculosis, is necessary for this effect. These results show that SP-A-mediated binding of M. tuberculosis to AMs significantly decreased RNI levels, suggesting that this may be one mechanism by which M. tuberculosis diminishes the cytotoxic response of activated AMs.  (+info)

Tuberculosis outbreaks in prison housing units for HIV-infected inmates--California, 1995-1996. (3/9979)

During 1995-1996, staff from the California departments of corrections and health services and local health departments investigated two outbreaks of drug-susceptible tuberculosis (TB). The outbreaks occurred in two state correctional institutions with dedicated HIV housing units. In each outbreak, all cases were linked by IS6110-based DNA fingerprinting of Mycobacterium tuberculosis isolates. This report describes the investigations of both outbreaks; the findings indicated that M. tuberculosis can spread rapidly among HIV-infected inmates and be transmitted to their visitors and prison employees, with secondary spread to the community.  (+info)

Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques. (4/9979)

The availability of DNA fingerprinting techniques for Mycobacterium tuberculosis has led to attempts to estimate the extent of recent transmission in populations, using the assumption that groups of tuberculosis patients with identical isolates ("clusters") are likely to reflect recently acquired infections. It is never possible to include all cases of tuberculosis in a given population in a study, and the proportion of isolates found to be clustered will depend on the completeness of the sampling. Using stochastic simulation models based on real and hypothetical populations, the authors demonstrate the influence of incomplete sampling on the estimates of clustering obtained. The results show that as the sampling fraction increases, the proportion of isolates identified as clustered also increases and the variance of the estimated proportion clustered decreases. Cluster size is also important: the underestimation of clustering for any given sampling fraction is greater, and the variability in the results obtained is larger, for populations with small clusters than for those with the same number of individuals arranged in large clusters. A considerable amount of caution should be used in interpreting the results of studies on clustering of M. tuberculosis isolates, particularly when sampling fractions are small.  (+info)

A train passenger with pulmonary tuberculosis: evidence of limited transmission during travel. (5/9979)

In January 1996, smear- and culture-positive tuberculosis (TB) was diagnosed for a 22-year-old black man after he had traveled on two U.S. passenger trains (29.1 hours) and a bus (5.5 hours) over 2 days. To determine if transmission had occurred, passengers and crew were notified of the potential exposure and instructed to undergo a tuberculin skin test (TST). Of the 240 persons who completed screening, 4 (2%) had a documented TST conversion (increase in induration of > or = 10 mm between successive TSTs), 11 (5%) had a single positive TST (> or = 10 mm), and 225 (94%) had a negative TST (< 10 mm). For two persons who underwent conversion, no other risk factors for a conversion were identified other than exposure to the ill passenger during train and/or bus travel. These findings support limited transmission of Mycobacterium tuberculosis from a potentially highly infectious passenger to other persons during extended train and bus travel.  (+info)

Site-directed spin labeling study of subunit interactions in the alpha-crystallin domain of small heat-shock proteins. Comparison of the oligomer symmetry in alphaA-crystallin, HSP 27, and HSP 16.3. (6/9979)

Site-directed spin labeling was used to investigate quaternary interactions along a conserved sequence in the alpha-crystallin domain of alphaA-crystallin, heat-shock protein 27 (HSP 27), and Mycobacterium tuberculosis heat-shock protein (HSP 16.3). In previous work, it was demonstrated that this sequence in alphaA-crystallin and HSP 27 forms a beta-strand involved in subunit contacts. In this study, the symmetry and geometry of the resulting interface were investigated. For this purpose, the pattern of spin-spin interactions was analyzed, and the number of interacting spins was determined in alphaA-crystallin and HSP 27. The results reveal a 2-fold symmetric interface consisting of two beta-strands interacting near their N termini in an antiparallel fashion. Remarkably, subunit interactions along this interface persist when the alpha-crystallin domains are expressed in isolation. Because this domain in alphaA-crystallin forms dimers and tetramers, it is inferred that interactions along this interface mediate the formation of a basic dimeric unit. In contrast, in HSP 16.3, spin-spin interactions are observed at only one site near the C terminus of the sequence. Furthermore, cysteine substitutions at residues flanking the N terminus resulted in the dissociation of the oligomeric structure. Analysis of the spin-spin interactions and size exclusion chromatography indicates a 3-fold symmetric interface. Taken together, our results demonstrate that subunit interactions in the alpha-crystallin domain of mammalian small heat-shock proteins assemble a basic building block of the oligomeric structure. Sequence divergence in this domain results in variations in the size and symmetry of the quaternary structure between distant members of the small heat-shock protein family.  (+info)

Comparison of synonymous codon distribution patterns of bacteriophage and host genomes. (7/9979)

Synonymous codon usage patterns of bacteriophage and host genomes were compared. Two indexes, G + C base composition of a gene (fgc) and fraction of translationally optimal codons of the gene (fop), were used in the comparison. Synonymous codon usage data of all the coding sequences on a genome are represented as a cloud of points in the plane of fop vs. fgc. The Escherichia coli coding sequences appear to exhibit two phases, "rising" and "flat" phases. Genes that are essential for survival and are thought to be native are located in the flat phase, while foreign-type genes from prophages and transposons are found in the rising phase with a slope of nearly unity in the fgc vs. fop plot. Synonymous codon distribution patterns of genes from temperate phages P4, P2, N15 and lambda are similar to the pattern of E. coli rising phase genes. In contrast, genes from the virulent phage T7 or T4, for which a phage-encoded DNA polymerase is identified, fall in a linear curve with a slope of nearly zero in the fop vs. fgc plane. These results may suggest that the G + C contents for T7, T4 and E. coli flat phase genes are subject to the directional mutation pressure and are determined by the DNA polymerase used in the replication. There is significant variation in the fop values of the phage genes, suggesting an adjustment to gene expression level. Similar analyses of codon distribution patterns were carried out for Haemophilus influenzae, Bacillus subtilis, Mycobacterium tuberculosis and their phages with complete genomic sequences available.  (+info)

Fluoroquinolone action against clinical isolates of Mycobacterium tuberculosis: effects of a C-8 methoxyl group on survival in liquid media and in human macrophages. (8/9979)

When the lethal action of a C-8 methoxyl fluoroquinolone against clinical isolates of Mycobacterium tuberculosis in liquid medium was measured, the compound was found to be three to four times more effective (as determined by measuring the 90% lethal dose) than a C-8-H control fluoroquinolone or ciprofloxacin against cells having a wild-type gyrA (gyrase) gene. Against ciprofloxacin-resistant strains, the C-8 methoxyl group enhanced lethality when alanine was replaced by valine at position 90 of the GyrA protein or when aspartic acid 94 was replaced by glycine, histidine, or tyrosine. During infection of a human macrophage model by wild-type Mycobacterium bovis BCG, the C-8 methoxyl group lowered survival 20- to 100-fold compared with the same concentration of a C-8-H fluoroquinolone. The C-8 methoxyl fluoroquinolone was also more effective than ciprofloxacin against a gyrA Asn94 mutant of M. bovis BCG. In an M. tuberculosis-macrophage system the C-8 methoxyl group improved fluoroquinolone action against both quinolone-susceptible and quinolone-resistant clinical isolates. Thus, a C-8 methoxyl group enhances the bactericidal activity of quinolones with N1-cyclopropyl substitutions; these data encourage further refinement of fluoroquinolones as antituberculosis agents.  (+info)

  • All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. (genetics.org)
  • Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. (aku.edu)
  • and Mycobacterium tuberculosis ) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. (genetics.org)
  • To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. (genetics.org)
  • for estimating genetic relationships among M. tuberculosis strains and for studying relationships between strain genotype and patient phenotype. (genetics.org)
  • As with other bacterial diseases, tuberculosis is increasingly drug resistant, with strains resistant to two front-line drugs, isoniazid and rifampicin (multi-drug resistant), and additional resistance to an injectable antibiotic and a quinolone (extensive-drug resistant) killing now over 500 thousand patients out of a total of 1,800,000 deaths ( WHO, 2017 ). (elifesciences.org)
  • We evaluated the clinical usefulness of spoligotyping, a polymerase chain reaction-based method for simultaneous detection and typing of Mycobacterium tuberculosis strains, with acid-fast bacilli-positive slides from clinical specimens or mycobacterial cultures. (cdc.gov)
  • We sequenced the genomes of 21 strains representative of the global diversity and six major lineages of the M. tuberculosis complex (MTBC) at 40- to 90-fold coverage using Illumina next-generation DNA sequencing. (unibas.ch)
  • A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery. (ncbs.res.in)
  • The Mycobacterium tuberculosis complex CFP-10/ESAT-6 family proteins play essential but poorly defined roles in tuberculosis pathogenesis. (kent.ac.uk)
  • While intensive research efforts are addressing the pathogenesis, new drugs and vaccines are also necessary to explore into conceptual novel approaches for tuberculosis control. (biomedcentral.com)
  • yet, the functions of many proteins in M. tuberculosis remain unknown. (ncbs.res.in)
  • Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. (ncbs.res.in)
  • Analysis of the structure of the CFP-10.ESAT-6 complex and optimized amino acid sequence alignments of M. tuberculosis CFP-10/ESAT-6 family proteins revealed that residues involved in the intramolecular contacts between helices are conserved across the CFP-10/ ESAT-6 family, but not those involved in primarily intermolecular contacts. (kent.ac.uk)
  • In this paper, we now characterize the processing pathway in an additional six M. tuberculosis epitopes from four proteins in human dendritic cells. (elsevier.com)
  • Antisera raised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. (elsevier.com)
  • Furthermore, we found that over-expression of CwlM stimulated M. tuberculosis survival in activated macrophages. (findaphd.com)
  • Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis, is a secreted protein. (elsevier.com)
  • Mycobacterium tuberculosis is the most successful human pathogen worldwide, responsible for 3 million deaths each year and extensive morbidity and mortality ( W orld H ealth O rganization 1998 ). (genetics.org)
  • Mycobacterium tuberculosis is an obligate human pathogen capable of persisting in individual hosts for decades. (unibas.ch)
  • It is known, that the sugars present in some Mycobacterium tuberculosis glycoproteins play an important role in both humoral and cellular immune response against the pathogen. (biomedcentral.com)
  • The Mycobacterium tuberculosis Rv2686c-Rv2687c-Rv2688c operon, encoding an ABC transporter, conferred resistance to ciprofloxacin and, to a lesser extent, norfloxacin, moxifloxacin, and sparfloxacin to Mycobacterium smegmatis. (pasteur.fr)
  • The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease. (scielo.br)
  • An essential requirement for the effective control of tuberculosis (TB), a major health care problem worldwide, is the characterization of the Mycobacterium tuberculosis (Mtb) antigens (Ags) that are recognized by T cells. (scielo.br)
  • We explore how Mycobacterium tuberculosis utilises amino acids as nitrogen sources, using a combination of bacterial physiology and stable isotope tracing coupled to mass spectrometry metabolomics methods. (elifesciences.org)
  • In the present work, we investigated the feasibility of R. erythropolis as a host for the recombinant production of M. tuberculosis glycoproteins, Apa and the lipoglycoproteins PstS1 and LprG. (biomedcentral.com)
  • Tuberculosis remains a major global threat as it affects humans and production animals. (findaphd.com)
  • Although CD8 + T cells are elicited at high frequencies over the course of infection in both humans and mice, how phagosomal M. tuberculosis Ags are processed and presented by MHC class I molecules is poorly understood. (elsevier.com)
  • Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. (elsevier.com)
  • This test should not replace AFB smear and culture since they will determine if mycobacterium other than tuberculosis complex are present in addition to MTB complex and the culture is necessary to perform antimycobacterial susceptibility testing. (dlslab.com)
  • Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. (ncbs.res.in)
  • Nitric oxide (NO) has been long implicated in triggering dormancy in mycobacteria, while serine threonine protein kinases PknB and PknG have been shown to be critical for reactivation from dormancy and regulation of central metabolism. (findaphd.com)
  • Among human immunodeficiency virus (HIV)-infected persons, those who react against purified protein derivative (PPD) have higher risk of tuberculosis. (elsevier.com)
  • The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. (elsevier.com)
  • Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides. (elsevier.com)
  • According to Worth Health Organization, tuberculosis claims about 2 million lives every year with almost one-third of the human population infected with M. tuberculosis , a microorganism that develops resistance to virtually all new drugs produced to fight it. (biomedcentral.com)
  • Upon encountering the host-relevant environment of acidic pH, Mycobacterium tuberculosis (Mtb) slows and even arrests growth in a process that requires remodeling of central carbon metabolism. (calvin.edu)
  • Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. (elsevier.com)
  • Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic infection in most individuals. (elsevier.com)
  • We have previously characterized the presentation of three HLA-I epitopes from M. tuberculosis and shown that these Ags are processed in the cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. (elsevier.com)
  • However, studies have shown that it will also benefit patients with high suspicion of tuberculosis, but with negative AFB smear results. (dlslab.com)
  • In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. (elsevier.com)
  • Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. (elsevier.com)
  • Forty HIV-negative healthy subjects and 40 HIV-negative tuberculosis patients were evaluated as controls. (elsevier.com)
  • WHO estimates that one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), forming a huge latent Mtb global reservoir. (www.gov.uk)
  • Most infections do not have symptoms, in which case it is known as latent tuberculosis . (answersdrive.com)
  • This study represents the first in-depth analysis of nitrogen source utilisation by M. tuberculosis and reveals a flexible metabolic network with characteristics that are likely a product of evolution in the human host. (elifesciences.org)
  • This suggests that M. tuberculosis has evolved to be very flexible in its dietary habits, which may explain why these bacteria can thrive in the varied environments within the human body. (elifesciences.org)
  • Little is known about the metabolic state of Mycobacterium tuberculosis (Mtb) inside the phagosome, a compartment inside phagocytes for killing pathogens and other foreign substances. (wur.nl)