For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
176
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      599
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Advances in Key Drug Target Identification and New Drug Development for Tuberculosis

      review-article
      Author(s): , ,
      Publication date (Electronic):
      Journal: BioMed Research International
      Publisher: Hindawi

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Tuberculosis (TB) is a severe infectious disease worldwide. The increasing emergence of drug-resistant Mycobacterium tuberculosis ( Mtb) has markedly hampered TB control. Therefore, there is an urgent need to develop new anti-TB drugs to treat drug-resistant TB and shorten the standard therapy. The discovery of targets of drug action will lay a theoretical foundation for new drug development. With the development of molecular biology and the success of Mtb genome sequencing, great progress has been made in the discovery of new targets and their relevant inhibitors. In this review, we summarized 45 important drug targets and 15 new drugs that are currently being tested in clinical stages and several prospective molecules that are still at the level of preclinical studies. A comprehensive understanding of the drug targets of Mtb can provide extensive insights into the development of safer and more efficient drugs and may contribute new ideas for TB control and treatment.

          Related collections

          Most cited references176

          • Record: found
          • Abstract: found
          • Article: not found

          Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

          S T Cole, R Brosch, J. Parkhill … (1998)
          Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
          Article 0 comments Cited 364 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis.

            G Mahairas, P. J. Sabo, M J Hickey … (1996)
            The live attenuated bacillus Calmette-Guérin (BCG) vaccine for the prevention of disease associated with Mycobacterium tuberculosis was derived from the closely related virulent tubercle bacillus, Mycobacterium bovis. Although the BCG vaccine has been one of the most widely used vaccines in the world for over 40 years, the genetic basis of BCG's attenuation has never been elucidated. We employed subtractive genomic hybridization to identify genetic differences between virulent M. bovis and M. tuberculosis and avirulent BCG. Three distinct genomic regions of difference (designated RD1 to RD3) were found to be deleted from BCG, and the precise junctions and DNA sequence of each deletion were determined. RD3, a 9.3-kb genomic segment present in virulent laboratory strains of M. bovis and M. tuberculosis, was absent from BCG and 84% of virulent clinical isolates. RD2, a 10.7-kb DNA segment containing a novel repetitive element and the previously identified mpt-64 gene, was conserved in all virulent laboratory and clinical tubercle bacilli tested and was deleted only from substrains derived from the original BCG Pasteur strain after 1925. Thus, the RD2 deletion occurred after the original derivation of BCG. RD1, a 9.5-kb DNA segment found to be deleted from all BCG substrains, was conserved in all virulent laboratory and clinical isolates of M. bovis and M. tuberculosis tested. The reintroduction of RD1 into BCG repressed the expression of at least 10 proteins and resulted in a protein expression profile almost identical to that of virulent M. bovis and M. tuberculosis, as determined by two-dimensional gel electrophoresis. These data indicate a role for RD1 in the regulation of multiple genetic loci, suggesting that the loss of virulence by BCG is due to a regulatory mutation. These findings may be applicable to the rational design of a new attenuated tuberculosis vaccine and the development of new diagnostic tests to distinguish BCG vaccination from tuberculosis infection.
            Article 0 comments Cited 220 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis.

              Sheshagiri Gaonkar, Vadim Makarov, V. Balasubramanian … (2009)
              New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB.
              Article 0 comments Cited 174 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Xueqiong Wu:
                ORCID: https://orcid.org/0000-0001-8894-1929
                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date Collection: 2022
                Publication date (Electronic): 25 February 2022
                Volume: 2022
                Electronic Location Identifier: 5099312
                Affiliations
                Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing 100091, China
                Author notes

                Academic Editor: Atef M. Al Attar

                Author information
                https://orcid.org/0000-0001-5068-0604
                https://orcid.org/0000-0002-0333-890X
                https://orcid.org/0000-0001-8894-1929
                Article
                DOI: 10.1155/2022/5099312
                PMC ID: 8896939
                PubMed ID: 35252448
                SO-VID: 764bff42-850c-4036-81d5-bc0913a92e0d
                Copyright © Copyright © 2022 Jie Mi et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 3 October 2021
                Date accepted : 14 February 2022
                Funding
                Funded by: General Subject Foundation of the 8 th Medical Center of PLA General Hospital
                Award ID: 2018MS-010
                Funded by: Beijing Science and Technology Committee Research Project Foundation of China
                Award ID: Z171100001717010
                Categories
                Subject: Review Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content599

                See all similar

                Cited by4

                See all cited by

                Most referenced authors2,616

                See all reference authors