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1.发明授权
公开(公告)号：US5783386A
公开(公告)日：1998-07-21
申请号：US363255
申请日：1994-12-23
申请人： William R. Jacobs, Jr. , Barry R. Bloom , Desmond Michael Collins , Geoffrey W. de Lisle , Lisa Pascopella , Riku Pamela Kawakami
发明人： William R. Jacobs, Jr. , Barry R. Bloom , Desmond Michael Collins , Geoffrey W. de Lisle , Lisa Pascopella , Riku Pamela Kawakami
摘要： Polynucleotides associated with virulence in mycobacteria, and particularly a fragment of DNA isolated from M. bovis that contains a region encoding a putative sigma factor. Also provided are methods for a DNA sequence or sequences associated with virulence determinants in mycobacteria, and particularly in M. tuberculosis and M. bovis. The invention also provides corresponding polynucleotides associated with avirulence in mycobacteria. In addition, the invention provides a method for producing strains with altered virulence or other properties which can themselves be used to identify and manipulate individual genes.
摘要翻译： 与分枝杆菌中的毒力相关的多核苷酸，特别是分离自牛分枝杆菌的DNA片段，其含有编码推定的西格玛因子的区域。 还提供了在分枝杆菌，特别是结核分枝杆菌和牛分枝杆菌中的DNA序列或与毒力决定簇相关的序列的方法。 本发明还提供了与分枝杆菌中无毒性相关的相应多核苷酸。 此外，本发明提供了一种用于产生具有改变的毒力或其他性质的菌株的方法，其本身可用于鉴定和操纵个体基因。
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2.发明授权Methods and compositions for detecting and treating mycobacterial infections using an INHA gene 失效使用INHA基因检测和治疗分枝杆菌感染的方法和组合物
公开(公告)号：US5686590A
公开(公告)日：1997-11-11
申请号：US241766
申请日：1994-05-12
申请人： William R. Jacobs, Jr. , Desmond Michael Collins , Asesh Banerjee , Geoffrey William de Lisle , Theresa Mary Wilson
发明人： William R. Jacobs, Jr. , Desmond Michael Collins , Asesh Banerjee , Geoffrey William de Lisle , Theresa Mary Wilson
CPC分类号： C07K14/35 , Y10S530/825
摘要： The embodiments of the invention are based upon the identification and characterization of genes that determine mycobacterial resistance to the antibiotic isoniazid (INH) and its analogs. These genes, termed inhA, encode a polypeptide, InhA, that is the target of action of mycobacteria for isoniazid. The sequences of wild-type INH-sensitive as well as allelic or mutant INH-resistant inhA genes and their operons are provided. Also provided are isolated InhA polypeptides of both the INH-resistant and INH-sensitive types.
摘要翻译： 本发明的实施方案基于确定对抗生素异烟肼（INH）及其类似物的分枝杆菌抗性的基因的鉴定和表征。 这些称为inhA的基因编码多肽InhA，即分子异构体对异烟肼的作用目标。 提供了野生型INH敏感以及等位基因或突变INH抗性inhA基因及其操纵子的序列。 还提供了INH抗性和INH敏感型的分离的InhA多肽。
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公开(公告)号：US06372478B1
公开(公告)日：2002-04-16
申请号：US09314207
申请日：1999-05-19
申请人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
IPC分类号： C12N120
CPC分类号： A61K39/04 , A61K39/00 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12N2795/10022 , C12R1/32 , Y02A50/412 , Y02A50/476
摘要： 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). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US5968733A
公开(公告)日：1999-10-19
申请号：US14560
申请日：1998-01-28
申请人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
IPC分类号： G01N33/53 , A61K39/00 , A61K39/04 , A61K39/39 , A61P31/04 , A61P31/06 , A61P31/08 , A61P31/12 , A61P31/16 , A61P31/18 , A61P31/22 , A61P37/04 , A61P39/02 , C07K14/01 , C07K14/35 , C12N1/21 , C12N15/09 , C12N15/74 , C12N15/87 , C12P21/02 , C12R1/19 , C12R1/32 , C12R1/325 , C12R1/33 , C12R1/34 , G01N33/50 , C12Q1/70 , C07H21/04
CPC分类号： A61K39/04 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12R1/32 , A61K39/00 , C12N2795/10022
摘要： 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). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US06300061B1
公开(公告)日：2001-10-09
申请号：US08705557
申请日：1996-08-29
IPC分类号： C12Q168
CPC分类号： C07K14/005 , C07K14/35 , C12N7/00 , C12N15/74 , C12N2795/10322 , C12Q1/18 , C12Q1/6897 , G01N33/5695
摘要： 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.
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公开(公告)号：US5854055A
公开(公告)日：1998-12-29
申请号：US463942
申请日：1995-06-05
申请人： Barry R. Bloom , William R. Jacobs, Jr. , Ronald W. Davis , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , William R. Jacobs, Jr. , Ronald W. Davis , Richard A. Young , Robert N. Husson
IPC分类号： G01N33/53 , A61K39/00 , A61K39/04 , A61K39/39 , A61P31/04 , A61P31/06 , A61P31/08 , A61P31/12 , A61P31/16 , A61P31/18 , A61P31/22 , A61P37/04 , A61P39/02 , C07K14/01 , C07K14/35 , C12N1/21 , C12N15/09 , C12N15/74 , C12N15/87 , C12P21/02 , C12R1/19 , C12R1/32 , C12R1/325 , C12R1/33 , C12R1/34 , G01N33/50 , C12N15/64 , C12N15/66
CPC分类号： A61K39/04 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12R1/32 , A61K39/00 , C12N2795/10022
摘要： 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). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant plasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分解细菌宿主溶解的重组质粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US06270776B1
公开(公告)日：2001-08-07
申请号：US08454075
申请日：1995-05-30
申请人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
IPC分类号： A61K3500
CPC分类号： A61K39/04 , A61K39/00 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12N2795/10022 , C12R1/32 , Y02A50/412 , Y02A50/476
摘要： 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). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US06225066B1
公开(公告)日：2001-05-01
申请号：US09426436
申请日：1999-10-25
IPC分类号： C12Q168
CPC分类号： C07K14/005 , C07K14/35 , C12N7/00 , C12N15/74 , C12N2795/10322 , C12Q1/18 , C12Q1/6897 , G01N33/5695
摘要： 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.
摘要翻译： 本发明涉及分枝杆菌物种特异性报道分枝杆菌噬菌体（报道分枝杆菌噬菌体），产生所述报道分枝杆菌噬菌体的方法和所述报道分枝杆菌噬菌体用于快速诊断分枝杆菌感染和评估临床样品中分枝杆菌菌株药物敏感性的用途。 特别地，本发明涉及荧光素酶报道分枝杆菌噬菌体的生产和使用以诊断结核病。 分枝杆菌种特异性报道分枝杆菌噬菌体包含含有报道基因和转录促进剂的分枝杆菌种特异性分枝杆菌噬菌体。 当报道分枝杆菌噬菌体与可能含有感兴趣分枝杆菌的临床样品一起孵育时，如果样品含有感兴趣的分枝杆菌，报告基因的基因产物将被表达，从而诊断分枝杆菌感染。
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公开(公告)号：US5504005A
公开(公告)日：1996-04-02
申请号：US361944
申请日：1989-06-05
申请人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
IPC分类号： G01N33/53 , A61K39/00 , A61K39/04 , A61K39/39 , A61P31/04 , A61P31/06 , A61P31/08 , A61P31/12 , A61P31/16 , A61P31/18 , A61P31/22 , A61P37/04 , A61P39/02 , C07K14/01 , C07K14/35 , C12N1/21 , C12N15/09 , C12N15/74 , C12N15/87 , C12P21/02 , C12R1/19 , C12R1/32 , C12R1/325 , C12R1/33 , C12R1/34 , G01N33/50 , C12N15/64 , C12N15/66
CPC分类号： A61K39/04 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12R1/32 , A61K39/00 , C12N2795/10022
摘要： 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). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US06821769B2
公开(公告)日：2004-11-23
申请号：US09918951
申请日：2001-07-31
IPC分类号： C12N112
CPC分类号： C07K14/35 , A61K2039/53 , C12N15/74 , Y02A50/412 , Y02A50/466 , Y10S435/863 , Y10S435/864 , Y10S435/865 , Y10S435/866
摘要： 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.
摘要翻译： 本发明涉及由通过抑制细胞壁生物合成起作用的广泛类型的抗生素诱导的分枝杆菌iniB，iniA和iniC基因的鉴定，克隆，测序和表征，包括第一线抗结核剂，异烟肼和乙胺丁醇。 本发明提供纯化和分离的iniB，iniA，iniC和iniB启动子核酸，其可以包含iniBAC操纵子，以及这些核酸的突变形式。 本发明还提供了一种或多种与iniB，iniA，iniC和iniB启动子核酸及其混合物特异性杂交的单链核酸探针，其可以配制在试剂盒中，并用于诊断耐药性 分枝杆菌菌株。 本发明还提供了利用iniB启动子的诱导来筛选和鉴定对结核分枝杆菌有效的药物的方法。
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