Abstract: A genetically modified mammalian cell and genetically modified mammalian cell line comprise a recombination sequence inserted in a target locus on a chromosome of the mammalian cell genome, wherein the recombination sequence comprises Bxb1attB sequence from Mycobacterium smegmatis. A transgenic mammalian cell and transgenic mammalian cell line comprise a heterologous nucleic acid stably integrated in a target locus on a chromosome of the mammalian genome, wherein the heterologous nucleic comprises a heterologous gene configured for expression by the transgenic mammalian cell.

Abstract: Provided are attenuated strains of M. tuberculosis and M. bovis BCG which are double auxotrophic mutants with genes knocked out in the biosynthetic pathways for arginine and methionine, and compositions and methods of use thereof.

Abstract: Provided are antibodies and antigen-binding fragments which bind to herpes simplex virus-2 (HSV-2), methods of use employing the antibodies and/or antigen-binding fragments, and pharmaceutical compositions comprising the antibodies and/or antigen-binding fragments.

Abstract: A genetically modified mammalian cell and genetically modified mammalian cell line comprise a recombination sequence inserted in a target locus on a chromosome of the mammalian cell genome, wherein the recombination sequence comprises Bxb1attB sequence from Mycobacterium smegmatis. A transgenic mammalian cell and transgenic mammalian cell line comprise a heterologous nucleic acid stably integrated in a target locus on a chromosome of the mammalian genome, wherein the heterologous nucleic comprises a heterologous gene configured for expression by the transgenic mammalian cell.

Abstract: Provided are attenuated strains of M. tuberculosis and M. bovis BCG which are double auxotrophic mutants with genes knocked out in the biosynthetic pathways for arginine and methionine, and compositions and methods of use thereof.

Abstract: The present invention addresses a need for improved methods of treating M. tuberculosis infection using enhancers of respiration, and compositions for treating tuberculosis as well as assays for identifying novel agents for treating M. tuberculosis infection.

Abstract: Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant mycobacterium, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.

Abstract: The present invention provides methods for determining a putative antibacterial, the methods comprising determining whether the putative antibacterial inhibits GlgE or Rv3032. The present invention also provides the antibacterial, the pharmaceutical composition and the method of making the antibacterial as well as a method of treating a subject infected with a bacterial comprising administration of the antibacterial.

Abstract: Provided are recombinant mycobacteria having a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a mycobacterium. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinant mycobacterium using the nlaA gene or the nuoG gene.

Abstract: Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant mycobacterium, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.

Abstract: Provided are mycobacteria comprising (a) a mutation that is not in a SecA2 gene that attenuates the virulence of the mycobacteria in a mammalian host, and (b) a mutation in a SecA2 gene that eliminates SecA2 activity. Also provided are mycobacteria that comprise a mutation in a SecA2 gene that eliminates SecA2 activity, where the mycobacteria are not Mycobacterium tuberculosis or Mycobacterium smegmatis. Additionally provided are methods of inducing an immune response in a mammal and methods of inducing an immune response to a pathogenic mycobacterium in a human using the above mycobacterial mutants.

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: Provided are recombinant mycobacteria expressing an HIV-1 antigen and a malarial antigen. Also provided are Mycobacterium smegmatis expressing an HIV-1 antigen. Further provided are vaccines capable of inducing an immune response in a mammal against HIV-1 and the malarial pathogen. Additionally provided are methods of inducing an immune response in a mammal against HIV-1 and a malarial pathogen. Also provided are methods of inducing an immune response in a mammal against HIV-1. The methods comprise infecting the mammal with any of the above-described mycobacteria.

Abstract: The present invention provides methods for determining a putative antibacterial, the methods comprising determining whether the putative antibacterial inhibits GlgE or Rv3032. The present invention also provides the antibacterial, the pharmaceutical composition and the method of making the antibacterial as well as a method of treating a subject infected with a bacterial comprising administration of the antibacterial.

Abstract: Provided are mycobacteria comprising a recombinant gene operably liked to a mammalian promoter that directs expression of the recombinant gene from a mammalian cell. Also provided are mammalian cells comprising the above mycobacteria. Additionally provided are mycobacterial plasmids capable of replication in a mycobacterium. Further provided are methods of expressing a recombinant gene in a mammalian cell.

Abstract: Provided are recombinant mycobacteria having a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a mycobacterium. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinant mycobacterium using the nlaA gene or the nuoG gene.

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: Provided are mycobacteria comprising (a) a mutation that is not in a SecA2 gene that attenuates the virulence of the mycobacteria in a mammalian host, and (b) a mutation in a SecA2 gene that eliminates SecA2 activity. Also provided are mycobacteria that comprise a mutation in a SecA2 gene that eliminates SecA2 activity, where the mycobacteria are not Mycobacterium tuberculosis or Mycobacterium smegmatis. Additionally provided are methods of inducing an immune response in a mammal and methods of inducing an immune response to a pathogenic mycobacterium in a human using the above mycobacterial mutants.

Abstract: This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.

Abstract: A mutated mycobacterium selected from the class consisting of mutated M. bovis-BCG, mutated M. tuberculosis, and mutated M. leprae. The mutation of M. bovis-BCG, M. tuberculosis, or M. leprae is preferably effected through an insertional mutation of a mycobacterial gene. The insertional mutagenesis may be effected, for example, through illegitimate recombination or by a mycobacterial transposon. Such mutated mycobacteria may then be transformed with an expression vector(s) containing a complement gene to the gene which is mutated, and preferably also including a heterologous gene.