State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach
Tuberculosis remains one of the causes of death from a single infectious bacterium. The inappropriate use of antibiotics and patients’ non-compliance among other factors drive the emergence of drug-resistant tuberculosis. Multidrug-resistant and extensively drug-resistant strains of tuberculosis pos...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Drug Discovery |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fddsv.2023.1254656/full |
| _version_ | 1797681935850405888 |
|---|---|
| author | Adetutu Akinnuwesi Samuel Egieyeh Ruben Cloete |
| author_facet | Adetutu Akinnuwesi Samuel Egieyeh Ruben Cloete |
| author_sort | Adetutu Akinnuwesi |
| collection | DOAJ |
| description | Tuberculosis remains one of the causes of death from a single infectious bacterium. The inappropriate use of antibiotics and patients’ non-compliance among other factors drive the emergence of drug-resistant tuberculosis. Multidrug-resistant and extensively drug-resistant strains of tuberculosis pose significant challenges to current treatment regimens, as their reduced efficacy against these strains limits successful patient outcomes. Furthermore, the limited effectiveness and associated toxicity of second-line drugs further compound the issue. Moreover, the scarcity of novel pharmacological targets and the subsequent decline in the number of anti-TB compounds in the drug development pipeline has further hindered the emergence of new therapies. As a result, researchers need to develop innovative approaches to identify potential new anti-TB drugs. The evolution of technology and the breakthrough in omics data allow the use of computational biology approaches, for example, metabolomic analysis to uncover pharmacological targets for structured-based drug design. The role of metabolism in pathogen development, growth, survival, and infection has been established. Therefore, this review focuses on the M. tb metabolic network as a hub for novel target identification and highlights a step-by-step subtractive genomics approach for target prioritization. |
| first_indexed | 2024-03-11T23:52:13Z |
| format | Article |
| id | doaj.art-80456377bf34440ca70adfdd67035f7c |
| institution | Directory Open Access Journal |
| issn | 2674-0338 |
| language | English |
| last_indexed | 2024-03-11T23:52:13Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Drug Discovery |
| spelling | doaj.art-80456377bf34440ca70adfdd67035f7c2023-09-19T06:38:49ZengFrontiers Media S.A.Frontiers in Drug Discovery2674-03382023-09-01310.3389/fddsv.2023.12546561254656State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approachAdetutu Akinnuwesi0Samuel Egieyeh1Ruben Cloete2South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South AfricaSchool of Pharmacy, University of the Western Cape, Cape Town, South AfricaSouth African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South AfricaTuberculosis remains one of the causes of death from a single infectious bacterium. The inappropriate use of antibiotics and patients’ non-compliance among other factors drive the emergence of drug-resistant tuberculosis. Multidrug-resistant and extensively drug-resistant strains of tuberculosis pose significant challenges to current treatment regimens, as their reduced efficacy against these strains limits successful patient outcomes. Furthermore, the limited effectiveness and associated toxicity of second-line drugs further compound the issue. Moreover, the scarcity of novel pharmacological targets and the subsequent decline in the number of anti-TB compounds in the drug development pipeline has further hindered the emergence of new therapies. As a result, researchers need to develop innovative approaches to identify potential new anti-TB drugs. The evolution of technology and the breakthrough in omics data allow the use of computational biology approaches, for example, metabolomic analysis to uncover pharmacological targets for structured-based drug design. The role of metabolism in pathogen development, growth, survival, and infection has been established. Therefore, this review focuses on the M. tb metabolic network as a hub for novel target identification and highlights a step-by-step subtractive genomics approach for target prioritization.https://www.frontiersin.org/articles/10.3389/fddsv.2023.1254656/fullMycobacterium tuberculosisdrug discoverymetabolic pathwaysubtractive genomic analysismulti-drug resistance tuberculosischoke point enzymes |
| spellingShingle | Adetutu Akinnuwesi Samuel Egieyeh Ruben Cloete State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach Frontiers in Drug Discovery Mycobacterium tuberculosis drug discovery metabolic pathway subtractive genomic analysis multi-drug resistance tuberculosis choke point enzymes |
| title | State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| title_full | State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| title_fullStr | State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| title_full_unstemmed | State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| title_short | State-of-the-art strategies to prioritize Mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| title_sort | state of the art strategies to prioritize mycobacterium tuberculosis drug targets for drug discovery using a subtractive genomics approach |
| topic | Mycobacterium tuberculosis drug discovery metabolic pathway subtractive genomic analysis multi-drug resistance tuberculosis choke point enzymes |
| url | https://www.frontiersin.org/articles/10.3389/fddsv.2023.1254656/full |
| work_keys_str_mv | AT adetutuakinnuwesi stateoftheartstrategiestoprioritizemycobacteriumtuberculosisdrugtargetsfordrugdiscoveryusingasubtractivegenomicsapproach AT samuelegieyeh stateoftheartstrategiestoprioritizemycobacteriumtuberculosisdrugtargetsfordrugdiscoveryusingasubtractivegenomicsapproach AT rubencloete stateoftheartstrategiestoprioritizemycobacteriumtuberculosisdrugtargetsfordrugdiscoveryusingasubtractivegenomicsapproach |