Abstract: This invention relates to a novel mycobacterial protein named DES, which appears to share significant amino acid sequence homology with soluble stearoyl-ACP desaturases. The results of allelic exchange experiments, indicate that the des gene may be essential to the survival of mycobacteria. These results coupled with the surface localization, the unique structure of DES, and the fact this antigen is expressed in vivo, and DES protein induces a humoral response in human patients, indicate that the DES protein provides a new target for the design of anti-mycobacterial drugs. This invention provides methods of screening molecules that can inhibit the DES enzyme activity of purified DES protein, in order to identify antibiotic molecules that are capable of inhibiting the growth or survival of mycobacteria.

Abstract: The invention concerns recombinant vectors replicated in mycobacteria, a set of sequences coding for exported polypeptides detected by fusion with alkaline phosphatase, in particular one polypeptide, called DP428, of about 12 kD corresponding to an exported protein found in mycobacteria belonging to the Mycobacterium tuberculosis complex. The invention also concerns methods and kits for detecting in vitro the presence of a mycobacterium and in particular a mycobacterium belonging to the Mycobacterium tuberculosis complex in a biological sample using said polypeptides, their fragments or polynucleotides coding for the latter. The invention also concerns immunogenic or vaccine compositions for preventing and/or treating infections caused by mycobacteria and in particular a mycobacterium belonging to said complex, particularly tuberculosis.

Abstract: The construction of a mutant in the phoP gene by means of homologous recombination from a clinically isolated Mycobacterium tuberculosis reduces the virulence thereof in mouse bone marrow macrophage. Moreover, the phoP mutant reduces the virulence thereof in the experimental mouse model. Said phoP mutant can persist without being eliminated both in the macrophage and in the mouse. Mice inoculated with the phoP mutant are protected against M. tuberculosis infection. The use of mutants of mycobacteria in which the phoP gene or the genes regulated by phoP have been inactivated are candidates for vaccines against human and animal tuberculosis as well as possible recombinant vaccines against other pathogens.

Abstract: This invention relates to a novel mycobacterial protein named DES, which appears to share significant amino acid sequence homology with soluble stearoyl-ACP desaturases. The results of allelic exchange experiments, indicate that the des gene may be essential to the survival of mycobacteria. These results coupled with the surface localization, the unique structure of DES, and the fact this antigen is expressed in vivo, and DES protein induces a humoral response in human patients, indicate that the DES protein provides a new target for the design of anti-mycobacterial drugs. This invention provides methods of screening molecules that can inhibit the DES enzyme activity of purified DES protein, in order to identify antibiotic molecules that are capable of inhibiting the growth or survival of mycobacteria.

Abstract: The present invention pertains to polynucleotides derived from M. tuberculosis genes imparting resistance to antibiotics and chemically related compounds. This invention also relates to the use of the polynucleotides as oligonucleotide primers or probes for detecting M. tuberculosis strains that are resistant to antibiotics and related compounds in a biological sample. Kits containing the primers and probes are also provided.

Abstract: The invention concerns recombinant vectors replicated in mycobacteria, a set of sequences coding for exported polypeptides detected by fusion with alkaline phosphatase, in particular one polypeptide, called DP428, of about 12 kD corresponding to an exported protein found in mycobacteria belonging to the Mycobacterium tuberculosis complex. The invention also concerns methods and kits for detecting in vitro the presence of a mycobacterium and in particular a mycobacterium belonging to the Mycobacterium tuberculosis complex in a biological sample using said polypeptides, their fragments or polynucleotides coding for the latter. The invention also concerns immunogenic or vaccine compositions for preventing and/or treating infections caused by mycobacteria and in particular a mycobacterium belonging to said complex, particularly tuberculosis.

Abstract: The use of genetic methodology based on the fusion of the proteins with the alcaline phosphatase (Lim et al., 1995) has allowed the isolation of a new exported protein of M. tuberculosis. In the present article, first of all the isolation of a gene encoding this exported protein called DES is described as well as its characterization and its destribution among the different microbacterial species. It is notably shown that the protein has in its primary sequence amino acids only found at the level of active sites of enzymes of class II diiron-oxo proteins family. Among the proteins of this family, DES protein of M. tuberculosis does not present significative homologies with stearoyl ACP desaturases. Secondly, the antigenic feature of this protein has been studied. For this, DES protein of M. tuberculosis has been overexpressed in E. coli under recombinant and purified protein from from this bacterium. The reactivity of tuberculous patients sera infected by M. tuberculosis or M.

Abstract: This invention relates to a novel mycobacterial protein named DES, which appears to share significant amino acid sequence homology with soluble stearoyl-ACP desaturases. The results of allelic exchange experiments, indicate that the des gene may be essential to the survival of mycobacteria. These results coupled with the surface localization, the unique structure of DES, and the fact this antigen is expressed in vivo, and DES protein induces a humoral response in human patients, indicate that the DES protein provides a new target for the design of anti-mycobacterial drugs. This invention provides methods of screening molecules that can inhibit the DES enzyme activity of purified DES protein, in order to identify antibiotic molecules that are capable of inhibiting the growth or survival of mycobacteria.

Abstract: The present invention pertains to polynucleotides derived from M. tuberculosis genes imparting resistance to antibiotics and chemically related compounds. This invention also relates to the use of the polynucleotides as oligonucleotide primers or probes for detecting M. tuberculosis strains that are resistant to antibiotics and related compounds in a biological sample. Kits containing the primers and probes are also provided.

Abstract: The invention concerns Mycobacterium strains whereof the erp gene is modified and a vaccine composition containing same. The modification of the erp gene decreases the virulence and the persistence of the Mycobacterium strains.

Abstract: The use of genetic methodology based on the fusion of the proteins with the alcaline phosphatase (Lim et al., 1995) has allowed the isolation of a new exported protein of M. tuberculosis. In the present article, first of all the isolation of a gene encoding this exported protein called DES is described as well as its characterization and its distribution among the different mycobacterial species. It is notably shown that the protein has in its primary sequence amino acids only found at the level of active sites of enzymes of class II diiron-oxo proteins family. Among the proteins of this family, DES protein of M. tuberculosis does not present significative homologies with stearoyl ACP desaturases. Secondly, the antigenic feature of this protein has been studied. For this, DES protein of M. tuberculosis has been overexpressed in E. coli under recombinant and purified protein form from this bacterium. The reactivity of tuberculous patients sera infected by M. tuberculosis or M.

Abstract: This invention relates to a novel mycobacterial protein named DES, which appears to share significant amino acid sequence homology with soluble stearoyl-ACP desaturases. The results of allelic exchange experiments, indicate that the des gene may be essential to the survival of mycobacteria. These results coupled with the surface localization, the unique structure of DES, and the fact this antigen is expressed in vivo, and DES protein induces a humoral response in human patients, indicate that the DES protein provides a new target for the design of anti-mycobacterial drugs. This invention provides methods of screening molecules that can inhibit the DES enzyme activity of purified DES protein, in order to identify antibiotic molecules that are capable of inhibiting the growth or survival of mycobacteria.

Abstract: Recombinant screening, cloning and/or expression vector characterized in that it replicates in mycobacteria and contains: 1) a mycobacteria functional replicon, 2) a selection marker, 3) a reporter cassette comprising: a) a multiple cloning site (polylinker), b) a transcription terminator which is active in mycobacteria and is located upstream of the polylinker, and c) a coding nucleotide sequence derived from a gene coding for an expression, export and/or secretion protein marker, the nucleotide sequence being deprived of its initiation codon and its regulating sequences. This vector is used for identification and expression of exporter polypeptides, such as the Mycobacterium tuberculosis P28 antigen.

Abstract: The invention concerns Mycobacterium strains whereof the erp gene is modified and a vaccine composition containing same. The modification of the erp gene decreases the virulence and the persistence of the Mycobacterium strains.

Abstract: The present invention is directed to a polynucleotide carrying an open reading frame coding for an antigenic polypeptide from Mycobacterium tuberculosis, named lhp, which is placed under the control of its own regulation signals which are functional in mycobacteria, specially in mycobacteria belonging to the Mycobacterium tuberculosis complex and also in fast growing mycobacteria such as Mycobacterium smegmatis. The invention is also directed to the polypeptide LHP encoded by lhp and most preferably to suitable antigenic portions of LHP as well as to oligomeric polypeptides containing more than one unit of LHP or an antigenic portion of LHP. The invention concerns also immunogenic and vaccine compositions containing a polypeptide or an oligomeric polypeptide such as defined above, as well as antibodies directed specifically against such polypeptides that are useful as diagnostic reagents.

Abstract: The present invention relates to the isolation of a new gene, des, which encodes a M. tuberculosis protein named DES. The des gene appears to be conserved among different Mycobacteria species. The amino acid sequence of the DES protein contains two sets of motifs that are characteristic of the active sites of enzymes from the class II diiron-oxo protein family. Among this family of proteins, DES shares significant homology with soluble stearoyl-ACP desaturases. DES is a highly antigenic protein, which is recognized by human sera from patients infected with M. tuberculosis and M. leprae but not by sera from tuberculous cattle. Thus, the DES protein provides a useful tool for the serodiagnostic analysis of tuberculosis.

Abstract: The present invention relates to the isolation of a new gene, des, which encodes a M. tuberculosis protein named DES. The des gene appears to be conserved among different Mycobacteria species. The amino acid sequence of the DES protein contains two sets of motifs that are characteristic of the active sites of enzymes from the class II diiron-oxo protein family. Among this family of proteins, DES shares significant homology with soluble stearoyl-ACP desaturases. DES is a highly antigenic protein, which is recognized by human sera from patients infected with M. tuberculosis and M. leprae but not by sera from tuberculous cattle. Thus, the DES protein provides a useful tool for the serodiagnostic analysis of tuberculosis.

Abstract: The present invention is directed to a polynucleotide carrying an open reading frame coding for an antigenic polypeptide from Mycobacterium tuberculosis, named lhp, which is placed under the control of its own regulation signals which are functional in mycobacteria, specially in mycobacteria belonging to the Mycobacterium tuberculosis complex and also in fast growing mycobacteria such as Mycobacterium smegmatis. The invention is also directed to the polypeptide LHP encoded by lhp and most preferably to suitable antigenic portions of LHP as well as to oligomeric polypeptides containing more than one unit of LHP or an antigenic portion of LHP. The invention concerns also immunogenic and vaccine compositions containing a polypeptide or an oligomeric polypeptide such as defined above, as well as antibodies directed specifically against such polypeptides that are useful as diagnostic reagents.

Abstract: Recombinant screening, cloning and/or expression vector characterized in that it replicates in mycobacteria and contains 1) a mycobacteria functional replicon; 2) a selection marker, 3) a reporter cassette comprising a) a multiple cloning site (polylinker) b) a transcription terminator which is active in mycobacteria and is located upstream of the polylinker, and c) a coding nucleotide sequence derived from a gene coding for an expression, export and/or secretion protein marker, the nucleotide sequence being deprived of its initiation codon and its regulating sequences. This vector is used for identification and expression of exporter polypeptides, such as the Mycobacterium tuberculosis P28 antigen.

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.