Abstract: The present invention relates to a bacterium attenuated by a mutation in at least one ABC transporter gene wherein the mutation renders the corresponding ABC transporter protein non-functional and wherein the attenuated bacterium persists in a subject.

Abstract: The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and nucleic acids encoding such compositions and fusion proteins. The compositions of the invention increase serological sensitivity of sera from individuals infected with tuberculosis, and methods for their use in the diagnosis, treatment, and prevention of tuberculosis infection.

Abstract: Methods of treating a mammal that is deficient in CD4+ and/or CD8+ lymphocytes are provided. The methods comprise inoculating the mammal with an attenuated mycobacterium in the M. tuberculosis complex. In these methods, the mycobacterium comprises two deletions, wherein a virulent mycobacterium in the M. tuberculosis complex having either deletion exhibits attenuated virulence. Use of these mycobacteria for the manufacture of a medicament for the treatment of mammals deficient in CD4+ and/or CD8+ lymphocytes is also provided.

Abstract: The present invention relates to a method of producing rough strains of a bacterium, such as Mycobacterium obuense, said method comprising exposing said bacterium to a sulfone and/or sulfonamide (such as 4,4?-Diaminodiphenyl sulfone or an analogue thereof). A rough strain of Mycobacterium obuense producible by said method and uses thereof. In particular, uses of a rough strain of Mycobacterium obuense deposited under the Budapest Treaty at the NCTC with the accession number NCTC 13365.

Abstract: The present invention allows a screening method for identifying novel drugs for the treatment of tuberculosis as well as a diagnostic method for identifying clinical strains that are resistant to these novel drugs. In particular, the present invention relates to a method for screening in vitro drug candidates for the treatment of tuberculosis by interfering with the arabinogalactan biosynthesis, the said method comprising a step of putting into contact a Mycobacterium tuberculosis cell culture overexpressing a protein that performs the transformation of decaprenyl-P-ribose to decaprenyl-P-arabinose and that can be encoded by rv3790 gene or homologues thereof or any open-reading artificial frame whose gene product is identical or homologue to Rv3790 protein, with a drug candidate and then evaluating the percentage of inhibition caused by the drug candidate against a control in an assay test, such as an antibacterial test or an enzymatic test.

Abstract: The present invention relates to the design of the Antisense-oligonucleotide complementary to the specific region of peptide deformylase gene from Mycobacterium tuberculosis. The use of this Antisense-oligonucleotide on mycobacterial culture inhibits the production of the peptide deformylase enzyme by hybridizing within the region, which is found to be responsible for maintaining stability as well as retaining the functionality of the enzyme and thus in turn affecting the growth of the cells. This invention also establishes the essentiality of the peptide deformylase enzyme in mycobacteria and claims it as a drug target in this microorganism.

Abstract: The present invention relates to a novel mycobacteria culture medium, particularly for mycobacteria of the Mycobacterium tuberculosis complex, that significantly reduces the culture isolation time and thus the time for diagnosing the mycobacteria, particularly those for tuberculosis. A culture medium according to the invention contains defibrinated blood, lecithin, and decomplemented fetal calf serum. The present invention also relates to a culture method and to a method for identifying mycobacteria, particularly bacteria of the Mycobacterium tuberculosis complex. The present invention also relates to a novel decontamination method through chlorhexidine treatment of biological samples in an isolation and mycobacteria culture medium, and to a method for determining by phenotype the sensitivity of mycobacteria to antibiotics by means of a solid culture medium according to the invention.

Abstract: The present invention is directed to reagents useful for generating immune responses to Mycobacterium tuberculosis and for diagnosing infection and disease in a subject that has been exposed to M. tuberculosis.

Abstract: The present invention provides a solid support for performing steps of isolation of cell or extraction and purification of nucleic acid, safely, easily, efficiently, and with high yield in the genetic test for investigating the presence of pathogenic bacterial infection. A solid support for binding with cell as an embodiment of the above-described solid support, comprises a polypeptide having capability of binding with my colic acid-containing glycolipid which is immobilized on the surface of a carrier. In addition, a solid support for binding with nucleic acid as another embodiment of the above-described solid support, comprises a polypeptide having capability of binding with nucleic acid which is immobilized on the surface of a carrier.

Abstract: Compositions and methods of producing vaccines, including methods wherein whole organism vaccines are provided with limited replication abilities, thereby increasing vaccine safety and efficacy, through the use of non-natural, unnatural, or non-naturally encoded amino acids.

Abstract: The present invention relates to the use of live mycobacterium of the M. tuberculosis complex for preparing a medicament, wherein the function of the zmp1-gene is inactivated, pharmaceutical compositions prepared from such mycobacteria as well as a method for the treatment and/or prophylaxis of a disease or medical condition using said pharmaceutical composition.

Abstract: The present invention relates to fusion proteins containing at least two Mycobacterium species antigens. In particular, it relates to nucleic acids encoding fusion proteins that include two or more individual M. tuberculosis antigens, which increase serological sensitivity of sera from individuals infected with tuberculosis, and methods for their use in the diagnosis, treatment, and prevention of tuberculosis infection.

Abstract: The present invention relates to an improved culture medium and method for the enhanced growth and detection of Mycobacterium growth. The invention further relates to an improved mycobacterial reagent system or kit that can be used for the enhanced growth and detection of Mycobacterium.

Abstract: The present invention relates to an improved culture medium and method for the enhanced growth and detection of Mycobacterium growth. The invention further relates to an improved mycobacterial reagent system or kit that can be used for the enhanced growth and detection of Mycobacterium.

Abstract: The present invention provides mutant Mycobacterium strains harboring a modified tyrosine phosphatase gene (mptpA or mptpB) wherein the mutant Mycobacterium strain is incapable of expressing the active tyrosine phosphatase. The invention provides a method for developing the said mutant strain from either Mycobacterium tuberculosis or Mycobacterium bovis. The mptpA or mptpB gene may be modified by replacing the internal sequences with an antibiotic resistance marker gene, which disrupts the expression of the active gene. The invention further provides a recombinant vector comprising the modified mptpA or mptpB which may be used to develop the mutant strains of mycobacteria. The invention provides a method to assess the role of tyrosine phosphatases MptpA and MptpB in the virulence and pathogenesis of Mycobacterium which can be used as potential targets for developing anti-tubercular drug.

Abstract: The invention provides polypeptides encoded by open reading frames present in the genome of Mycobacterium tuberculosis but absent from the genome of BCG and diagnostic and prophylactic methodologies using these polypeptides.

Abstract: A method is provided for identifying mycobacterial genes the expression of which is down-regulated during a stationary phase culture of mycobacteria under nutrient-starving conditions when compared with an exponential phase culture of mycobacteria under culture conditions that are not nutrient-starving and that support exponential growth of said mycobacteria. The described method optionally provides for identifying mycobacterial genes that are simultaneously down-regulated under low DOT conditions. The down-regulated genes of the present invention form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said down-regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

Abstract: Methods for diagnosing Mycobacterium tuberculosis infection in a human that include providing blood serum, contacting the serum with an Eis antigen fixed on a substrate, thereby forming complexes of Eis antigen with a human antibody that binds to the Eis antigen, contacting the antibody/Eis complexes with a labeled anti-human secondary antibody, and measuring a titer of the human antibody bound to the Eis antigen. In addition, statistically significant positive or negative diagnosis of infection with Mycobacterium tuberculosis is provided by comparing patient serum antibody titer with a second titer from a negative control blood sample.

Abstract: The present invention provides a growth medium and kit containing a nicotine analog and use of the same in a method for enhancing the growth of Mycobacterium avium subspecies paratuberculosis (MAP).

Abstract: The present invention relates to compositions of N-benzyl-3-(4-chlorophenyl)-2-[methyl-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]amino]-N-[3-(4-pyridyl)-1-[2-(4-pyridyl)ethyl]propyl]propanamide (Timcodar) useful for the treatment of patients with mycobacterium infections such as Mycobacterium tuberculosis. The invention also provides methods of treating patients with tuberculosis.

Abstract: A diagnostic kit for detecting pulmonary and extra pulmonary tuberculosis comprising a test card “TB Screen” coated with a hydrophobic material, antigen suspension, positive and negative control.

Abstract: A method of inducing latency in Mycobacterium permits preparation of an in vitro model system of latent mycobacterial infection. Latency is induced in a pure culture of Mycobacterium by exposing it to multiple stress conditions, including a low nutrient culture medium without glycerol, a low pH, a relatively high level of carbon dioxide and a relatively low gas phase oxygen level. An in vitro model of mycobacterial infection employs macrophages induced from THP1 cells which are then infected with Mycobacterium. The infected macrophages are grown under hypoxic conditions to induce latency in the mycobacteria. The in vitro model of infection is useful in evaluating compounds for activity against latent mycobacteria.

Abstract: A method of inducing latency in Mycobacterium permits preparation of an in vitro model system of latent mycobacterial infection. Latency is induced in a pure culture of Mycobacterium by exposing it to multiple stress conditions, including a low nutrient culture medium without glycerol, a low pH, a relatively high level of carbon dioxide and a relatively low gas phase oxygen level. An in vitro model of mycobacterial infection employs macrophages induced from THP1 cells which are then infected with Mycobacterium. The infected macrophages are grown under hypoxic conditions to induce latency in the mycobacteria. The in vitro model of infection is useful in evaluating compounds for activity against latent mycobacteria.

Abstract: A method of detecting an immune response to a paratuberculosis-specific antigen, comprising incubating a sample from a subject with the paratuberculosis-specific antigen and detecting the presence of an antibody in the sample as an indication of an immune response to the paratuberculosis-specific antigen. The antigen may be obtained from a novel M paratuberculosis strain JTC303. The antigen may be obtained from the JTC303 culture filtrate. Also provided are antibodies to the paratuberculosis-specific antigen, and a diagnostic kit for the detection of an immune response to a paratuberculosis-specific antigen in a mammal.

Abstract: Compositions and methods for identifying and using cis-regulatory and decoy sequences.

Abstract: The present invention provides nucleic acid molecules unique to M. paratuberculosis. The invention also provides the polypeptides encoded by the M. paratuberculosis-specific nucleic acid molecules of the invention, and antibodies having specific binding affinity for the polypeptides encoded by the M. paratuberculosis-specific nucleic acid molecules. The invention further provides for methods of detecting M. paratuberculosis in a sample using nucleic acid molecules, polypeptides, and antibodies of the invention. The invention additionally provides methods of preventing a M. paratuberculosis infection in an animal.

Abstract: Methods of preparing mutants of Mycobacterium tuberculosis with one or more disrupted genes are presented, where the disrupted genes include ctpV, rv0990c, rv0971c, and/or rv0348. Compositions containing mutants with attenuated virulence and pathogenesis, which are capable of stimulation of an immune response against tuberculosis, are described. Compositions and methods relating to immunogenic compositions, which include an attenuated M. tb strain in which the M. tb genome includes a disruption of at least one of the ctpV gene, the rv0990c gene, the rv0971c gene, and the rv0348 gene, are also provided.

Abstract: The invention relates to vaccine compositions composed of at least one Mycobacterium avium subspecies paratuberculosis (MAP) antigen, or attenuated or killed MAP for use in methods of immunizing a human against a MAP infection, preventing or treating a MAP infection, and preventing a human disease associated with a MAP infection.

Abstract: Particular aspects provide efficient allelic exchange methods to generate directed mutations within genes of slow-growing stains of mycobacteria (e.g., Mycobacterium avium subsp. paratuberculosis (Map), Map 10 or GFP-expressing Map K-10) using a phage-delivery system, and demonstrate high efficiency allelic exchange. Additional exemplary aspects provide non-naturally occurring slow-growing strains of mycobacteria (e.g., Map, M. bovis, M. tuberculosis) having at least one gene deletion (e.g., pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_1, leuD, and leuC, and deletion mutants at the orthologous loci of two known virulence genes in pathogenic mycobacteria (relA and pknG) and one gene related to colony morphology and biofilm formation in fast growing mycobacteria (lsr2) were made. Further aspects provide novel vaccines comprising such deletion mutants, or portions thereof, and methods for making said vaccines. Yet further aspects provide methods for protecting a mammal from virulent Map, M.

Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: Among the inventions disclosed herein are: nucleic acid expression systems for bacteria having an intracytoplasmic membrane system, including, for example, methanotrophic bacteria; recombinant nucleic acid constructs comprising a pmo promoter operably linked to an expressible nucleic acid; cloning vectors suitable for making recombinant nucleic acid constructs and methods for the production of proteins such as membrane proteins.

Abstract: The present invention describes the method of modulating MAPK pathways. Further more the invention describes the use of Mycobacterium w for modulation of MAPK pathway intermediates for treatment of MAPK mediated conditions.

Abstract: Gram negative bacterial virulence genes are identified, thereby allowing the identification of novel anti-bacterial agents that target these virulence genes and their products, and the provision of novel gram negative bacterial mutants useful in vaccines.

Abstract: The invention is directed compositions and methods related to bacterial cells physically associated with ceramide-like glycolipids. The invention allows for delivery of ceramide-like glycolipid adjuvants directly to the same cells that become infected with a bacterial vaccine. The compositions and methods of the present invention are useful for the prevention and treatment of diseases.

Abstract: Non-naturally occurring mycobacteria in the Mycobacterium tuberculosis complex are provided. These mycobacteria have a deletion of an RD1 region or a region controlling production of a vitamin, and exhibit attenuated virulence in a mammal when compared to the mycobacteria without the deletion. Also provided are non-naturally occurring mycobacteria that have a deletion of a region controlling production of lysine, and mycobacteria comprising two attenuating deletions. Vaccines comprising these mycobacteria are also provided, as are methods of protecting mammals from virulent mycobacteria using the vaccines. Also provided are methods of preparing these vaccines which include the step of deleting an RD1 region or a region controlling production of a vitamin or the amino acids leucine and lysine from a mycobacterium in the M. tuberculosis complex. Embodiments of these mycobacteria, vaccines and methods, encompassing mycobacteria comprising a leucine auxotrophy and a pantothenate auxotrophy, are also provided.

Abstract: The diagnosis of mycobacteria may be made by growing bacteria from clinical samples in a culture media. The culture medium enables rapid detection of mycobacterial growth by changing its color. It also differentiates mycobacterial growth from contamination by changing to a different color when other species of microorganisms grow. Different types of culture media may be obtained by adding antimicrobial drugs to either obtain a medium selective for mycobacteria or a medium for species differentiation or susceptibility testing of drugs.

Abstract: The invention relates to a method and system for the specific detection of a Mycobacterium tuberculosis (M. tuberculosis) in a biological sample, a difference being made, in particular between M. tuberculosis and other elements of M. tuberculosis complex, i.e., Mycobacterium bovis (M. bovis), Mycobacterium bovis BCG (M. bovis BCG), Mycobacterium africanum (M. africanum) and Mycobacterium microti (M. microti) based on a SNP in a narGHJI promoter.

Abstract: The present invention relates to an immunogenic polypeptide isolated from Mycobacterium avium subspecies paratuberculosis and variants of the polypeptide. The polypeptide and variants may be used in vaccines against Johne's disease and in methods for detection of the disease. Antibodies against the polypeptide or variants may be used in diagnostic tests for Johne's disease. Also included are polynucleotides encoding the polypeptide and variants, and methods for preparing these.

Abstract: The present invention relates to an isolated microorganism belonging to the genus Mycobacterium, characterized in that it comprises inactivating the gene Rv0757 that confers a PhoP? phenotype and inactivating a second gene that prevents the production of DIM (DIM? phenotype). Additionally, the present invention comprises the use of said microorganism for producing a vaccine for immunizing against or preventing tuberculosis.

Abstract: Non-naturally occurring mycobacteria in the Mycobacterium tuberculosis complex are provided. These mycobacteria have a deletion of an RD1 region or a region controlling production of a vitamin, and exhibit attenuated virulence in a mammal when compared to the mycobacteria without the deletion. Also provided are non-naturally occurring mycobacteria that have a deletion of a region controlling production of lysine, and mycobacteria comprising two attenuating deletions. Vaccines comprising these mycobacteria are also provided, as are methods of protecting mammals from virulent mycobacteria using the vaccines. Also provided are methods of preparing these vaccines which include the step of deleting an RD1 region or a region controlling production of a vitamin from a mycobacterium in the M. tuberculosis complex.

Abstract: The present invention relates to compositions and fusion proteins containing at least two Mycobacterium sp. antigens, and nucleic acids encoding such compositions and fusion proteins. The compositions of the invention increase serological sensitivity of sera from individuals infected with tuberculosis, and methods for their use in the diagnosis, treatment, and prevention of tuberculosis infection.

Abstract: Mycobacterium strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8+ T cell immune response are provided. The Mycobacterium strains are genetically engineered to express: a endosomolytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of the Mycobacterium from endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing such Mycobacterium strains.

Abstract: The present invention provides microorganisms, in which the activity of 4-hydroxybenzoate polyprenyltransferase or 2-octaprenylphenol?2-octaprenyl-6-methoxyphenol flavin reductase is reduced or lost, and which have an ability to produce lactic acid, in particular, microorganisms comprising a chromosomal DNA in which a gene encoding a protein having 4-hydroxybenzoate polyprenyltransferase activity or a protein having 2-octaprenylphenol?2-octaprenyl-6-methoxyphenol flavin reductase activity is partially or completely defective; and a process for producing lactic acid using the microorganisms.

Abstract: The present invention relates to a method of producing rough strains of a bacterium, such as Mycobacterium obuense, said method comprising exposing said bacterium to a sulfone and/or sulfonamide (such as 4,4?-Diaminodiphenyl sulfone or an analogue thereof). A rough strain of Mycobacterium obuense producible by said method and uses thereof. In particular, uses of a rough strain of Mycobacterium obuense deposited under the Budapest Treaty of NCTC with the accession number NCTC 13365.

Abstract: This invention relates to the use of a preparation of killed or non infectious Gram positive bacteria such as Gram positive facultative intracellular bacteria, for example mycobacteria, for the treatment of intestinal inflammatory syndromes such as Crohn's disease or ulcerative colitis.

Abstract: Mycobacteria such as M. tuberculosis and M. leprae are considered to be prototypical intracellular bacilli that have evolved strategies to enable growth in the intracellular phagosomes of the host cell. By contrast, we show that lysosomes rapidly fuse with the virulent M. tuberculosis and M. leprae— containing phagosomes of human monocyte-derived dendritic cells and macrophages. After 2 days, M. tuberculosis progressively translocate from phagolysosomes into the cytosol where they replicate. Cytosolic entry is also observed for M. leprae but not for the vaccine strain, M. bovis BCG, or killed mycobacteria, and is dependent upon secretion of the mycobacterial gene products CFP-IO and ESAT-6 of the RDI region. The present invention further provides means and methods for using these findings in therapeutic and immunogenic compositions.

Abstract: The present invention relates to methods, kits and assay system for detecting drug-resistant Mycobacterium tuberculosis of suspected patient. The system of the present invention largely reduces the whole process of drug-resistant M. tuberculosis detection in less than 5 hours.

Abstract: The present invention relates to a method of detecting the presence of a viable micro-organism of interest in a sample containing a contaminating micro-organism.

Abstract: The present invention relates to a method for killing or inhibiting cells of the genus Mycobacterium, in particular M. tuberculosis, with certain defensins.

Abstract: The invention relates to an non-pathogenic and/or attenuated bacterium which is capable of inducing apoptosis in macrophages.