Abstract: Compositions and methods for treatment and vaccination against tuberculosis are disclosed. In one aspect the compositions provided include at least two polypeptides that contain an immunogenic portion of a M. tuberculosis antigen or at least two DNA molecules encoding such polypeptides. In a second aspect, the compositions provided include a fusion protein comprising at least two polypeptides that contain an immunogenic portion of a M. tuberculosis antigen. Such compositions may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.

Abstract: Methods for the prevention and treatment of disorders, including disorders of the respiratory system, such as infection with mycobacteria such as M. tuberculosis or M. avium, sarcoidosis, asthma, allergic rhinitis and lung cancers are provided, such methods comprising administering a composition comprising derivatives of delipidated and deglycolipidated M vaccae cells.

Abstract: The invention discloses methods and materials for the utilization of chemically modified oligonucleotides in the treatment of drug-resistant bacterial infections including drug-resistant tuberculosis.

Abstract: The present invention relates to the discovery that the &agr;-dystroglycan receptor is required for Mycobacterium leprae entry into cells, assays for high throughput screening of drugs for use in treatments against leprosy, and methods for studying the role of the receptor in neurodegenerative and musculodegenerative diseases, and the like.

Abstract: The present invention provides a high-throughput screen for use in assaying for enzyme inhibitors of a target organism, comprising: a microorganism host in which an endogenous enzyme encoding gene has been replaced by a functionally complementing enzyme encoding gene from the target organism. The present invention also provides a method of identifying an inhibitor of a target organism enzyme, comprising the step of assaying a test inhibitor using a high-throughput screen comprising a microorganism host in which an endogenous enzyme encoding gene has been replaced by a functionally complementing enzyme encoding gene from the target organism.

Abstract: The present invention relates to enzymes produced by mutating the genes for a number of subtilases and expressing the mutated genes in suitable hosts are presented. The enzymes exhibit improved autoproteolytic stability in comparison to their wild type parent enzymes.

Abstract: This invention provides recombinant mycobacterium strains of pathogenic origin that have been attenuated by the inactivation of a gene coding for a metabolic protein, specifically a gene coding for a protein necessary for the biosynthesis of a purine or a pyrimidine base, and more precisely, the purC gene that codes for an enzyme of the metabolic pathway of purine biosynthesis. The recombinant mycobacterium of this invention have a reduced capacity to propagate in a mammalian host, but remain viable in the host for a period of time sufficient to induce an protective immune response against the natural pathogenic mycobacterium counterpart.

Abstract: Disclosed herein is a newly-identified DNA sequence from Mycobacterium kansasii designated KATS2. Also disclosed are methods, oligonucleotide probes, amplification primers, and kits for the detection of M. kansasii nucleic acids. M. kansasii-specific methods, probes, amplification primers, and kits are preferred.

Abstract: Compounds and methods for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more M. tuberculosis proteins and DNA molecules encoding such polypeptides. Such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.

Abstract: Disclosed are novel recombinant mutant strains of mycobacteria that are deficient for the synthesis or transport of dimycoserosalphthiocerol (“DIM”). The present invention also provides a method of producing a recombinant mutant mycobacterium that is deficient for the synthesis or transport of DIM, comprising mutating a nucleic acid responsible for the synthesis or transport of dimycoserosalphthiocerol, including a nucleic acid comprising the promoter for the pps operon, fadD28 or mmpL7. The present invention also provides a vaccine comprising a DIM mutant mycobacterium of the present invention, as well as a method for the treatment or prevention of tuberculosis in a subject using the vaccine.

Abstract: The present invention provides polypeptides comprising an immunogenic portion of a M. vaccae soluble protein and DNA molecules encoding such polypeptides, together with methods for their use in the diagnosis and treatment of mycobacterial infection. Methods for enhancing the immune response to an antigen including administration of M. vaccae culture filtrate or delipidated M. vaccae cells are also provided.

Abstract: A method of determining the presence of a paraffinophilic organism in a body specimen involves introducing portions of the body specimen into a plurality of receptacles (50-57) which contain a sterile broth and antibiotics. Subsequently, one paraffin coated slide (18) is introduced into each receptacle. After observing organism growth on the paraffin coated slides, at least one slide is subjected to an alcohol-acid fastness test to determine whether the organism is an alcohol-acid fast, an acid-fast organism or a non-acid-fast/non-alcohol-acid fast organism. If it is determined that an alcohol-acid fast organism is present on the first slide, a tellurite reduction assay is performed on a second slide to determine the possibility of a presence of paraffinophilic organism on the second slide.

Abstract: A carbohydrate complex, which is a mixture of low molecular-weight polysaccharides of an arabinomannan structure extracted from Mycobacterium tuberculosis, is highly effective in treating various cancer patients without incurring any adverse side effects.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: The present invention provides a method for high frequency of allelic exchange in the slow-growing mycobacteria using in vitro generated specialized transducing mycobacteriophages, as well as the recombinant slow-growing mycobacteria generated using the disclosed method. A transducing mycobacteriophage of the present invention comprises a conditional mycobacteriophage containing an E. coli bacteriophage lambda cosmid inserted into a non-essential region of the mycobacteriophage, said cosmid containing a mutated DNA substrate which is homologous to a wildtype nucleic acid sequence of a slow-growing mycobacterium. When slow-growing mycobacteria infected with the conditional transducing phage are cultured under conditions wherein the conditional transducing phage does not replicate, the mutated DNA substrate is incorporated into the chromosomal DNA of the slow-growing mycobacteria by homologous recombination, thereby generating the recombinant slow-growing mycobacteria of the present invention.

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: This invention provides recombinant mycobacterium strains of pathogenic origin that have been attenuated by the inactivation of a gene coding for a metabolic protein, specifically a gene coding for a protein necessary for the biosynthesis of a purine or a pyrimidine base, and more precisely, the purC gene that codes for an enzyme of the metabolic pathway of purine biosynthesis. The recombinant mycobacterium of this invention have a reduced capacity to propagate in a mammalian host, but remain viable in the host for a period of time sufficient to induce an protective immune response against the natural pathogenic mycobacterium counterpart.

Abstract: This invention relates to a Mycobacterium tuberculosis specific DNA fragment containing IS like and repetitive sequences, a method of production of such DNA fragment and the use of such DNA fragment, for example, to rapidly diagnose Mycobacterium tuberculosis infection in clinical samples, and to identify clinical isolates of Mycobacterium tuberculosis. The DNA fragment may be used to determine information about the epidemiology of Mycobacterium tuberculosis infection.

Abstract: A mycobacteria transformed with an antigen-encoding gene, such as nef, under the control of a Streptomyces stress-responsive promoter, such as the S. albus groES/groEL1 promoter, and preferably associated with a synthetic ribosome binding site. The recombinant mycobacteria can be used as a vaccine against, for example, a pathogen which carries the antigen.

Abstract: The invention relates to the nucleic acid sequence and amino acid sequence of dihydrofolate reductase (DHFR) from mycobacteria and to expression of recombinant DHFR protein. Utilizing the recombinant protein, novel therapies and diagnostic strategies can be developed and selective antimycobacterial compositions can be designed and utilized to treat mycobacterial infections in patients. This invention includes all or portions of novel recombinant nucleic acids encoding DHFR for mycobacteria such as M. avium, to novel recombinant DHFR peptides produced by such sequences, and to vaccines, diagnostic kits, cells and therapies utilizing these peptides and nucleic acid sequences. The present invention relates to methods for using the sequences of the present invention to develop drugs specific to M. avium and other mycobacteria, to identify and sequence corresponding sequences in species other than M. avium, as well as diagnostic and treatment methods incorporating the disclosed sequences and peptides.

Abstract: Multimeric hybrid genes encoding the corresponding chimeric protein comprise a gene sequence coding for an antigenic region of a protein from a first pathogen linked to a gene sequence coding for an antigenic region of a protein from a second pathogen. The pathogens particularly are parainfluenza virus (PIV) and respiratory syncytial virus (RSV). A single recombinant immunogen is capable of protecting infants and similar susceptible individuals against diseases caused by both PIV and RSV.

Abstract: This invention relates to mycobacterial species-specific reporter mycobacteriophages (reporter mycobacteriophages), methods of producing said reporter mycobacteriophages and the use of said reporter mycobacteriophages for the rapid diagnosis of mycobacterial infection and the assessment of drug susceptibilities of mycobacterial strains in clinical samples. In particular, this invention is directed to the production and use of luciferase reporter mycobacteriophages to diagnose tuberculosis. The mycobacterial species-specific reporter mycobacteriophages comprise mycobacterial species-specific mycobacteriophages which contain reporter genes and transcriptional promoters therein. When the reporter mycobacteriophages are incubated with clinical samples which may contain the mycobacteria of interest, the gene product of the reporter genes will be expressed if the sample contains the mycobacteria of interest, thereby diagnosing mycobacterial infection.

Abstract: The present invention refers in general to novel recombinant mycobacteria that are auxotrophic for diaminopimelate. In particular, this invention relates to novel auxotrophic recombinant mycobacteria, to methods of making the mycobacteria, and to uses of the mycobacteria to deliver vaccines. This invention also provides for uses of the mycobacteria in drug screening processes.

Abstract: The present invention relates to a DNA molecule conferring on Mycobacterium tuberculosis resistance to antimicrobial reactive oxygen intermediates and reactive nitrogen intermediates. The protein encoded by this DNA molecule is useful in vaccines to prevent invention by Mycobacterium tuberculosis, while the antibodies raised against this protein can be employed in passively immunizing those already infected by the organism. Both these proteins and antibodies may be utilized in diagnostic assays to detect Mycobacterium tuberculosis in tissue or bodily fluids. The protein or polypeptide is also useful as a therapeutic in treating conditions mediated by the production of reactive oxygen intermediates and nitrogen intermediates.