Type IA Topoisomerases as Targets for Infectious Disease Treatments
Infectious diseases are one of the main causes of death all over the world, with antimicrobial resistance presenting a great challenge. New antibiotics need to be developed to provide therapeutic treatment options, requiring novel drug targets to be identified and pursued. DNA topoisomerases control...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/9/1/86 |
| _version_ | 1797542766047133696 |
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| author | Ahmed Seddek Thirunavukkarasu Annamalai Yuk-Ching Tse-Dinh |
| author_facet | Ahmed Seddek Thirunavukkarasu Annamalai Yuk-Ching Tse-Dinh |
| author_sort | Ahmed Seddek |
| collection | DOAJ |
| description | Infectious diseases are one of the main causes of death all over the world, with antimicrobial resistance presenting a great challenge. New antibiotics need to be developed to provide therapeutic treatment options, requiring novel drug targets to be identified and pursued. DNA topoisomerases control the topology of DNA via DNA cleavage–rejoining coupled to DNA strand passage. The change in DNA topological features must be controlled in vital processes including DNA replication, transcription, and DNA repair. Type IIA topoisomerases are well established targets for antibiotics. In this review, type IA topoisomerases in bacteria are discussed as potential targets for new antibiotics. In certain bacterial pathogens, topoisomerase I is the only type IA topoisomerase present, which makes it a valuable antibiotic target. This review will summarize recent attempts that have been made to identify inhibitors of bacterial topoisomerase I as potential leads for antibiotics and use of these inhibitors as molecular probes in cellular studies. Crystal structures of inhibitor–enzyme complexes and more in-depth knowledge of their mechanisms of actions will help to establish the structure–activity relationship of potential drug leads and develop potent and selective therapeutics that can aid in combating the drug resistant bacterial infections that threaten public health. |
| first_indexed | 2024-03-10T13:35:09Z |
| format | Article |
| id | doaj.art-b8623b177f4341dc84be7e5f0ba5c5a4 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T13:35:09Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-b8623b177f4341dc84be7e5f0ba5c5a42023-11-21T07:39:26ZengMDPI AGMicroorganisms2076-26072021-01-01918610.3390/microorganisms9010086Type IA Topoisomerases as Targets for Infectious Disease TreatmentsAhmed Seddek0Thirunavukkarasu Annamalai1Yuk-Ching Tse-Dinh2Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USADepartment of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USADepartment of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USAInfectious diseases are one of the main causes of death all over the world, with antimicrobial resistance presenting a great challenge. New antibiotics need to be developed to provide therapeutic treatment options, requiring novel drug targets to be identified and pursued. DNA topoisomerases control the topology of DNA via DNA cleavage–rejoining coupled to DNA strand passage. The change in DNA topological features must be controlled in vital processes including DNA replication, transcription, and DNA repair. Type IIA topoisomerases are well established targets for antibiotics. In this review, type IA topoisomerases in bacteria are discussed as potential targets for new antibiotics. In certain bacterial pathogens, topoisomerase I is the only type IA topoisomerase present, which makes it a valuable antibiotic target. This review will summarize recent attempts that have been made to identify inhibitors of bacterial topoisomerase I as potential leads for antibiotics and use of these inhibitors as molecular probes in cellular studies. Crystal structures of inhibitor–enzyme complexes and more in-depth knowledge of their mechanisms of actions will help to establish the structure–activity relationship of potential drug leads and develop potent and selective therapeutics that can aid in combating the drug resistant bacterial infections that threaten public health.https://www.mdpi.com/2076-2607/9/1/86topoisomeraseantimicrobial resistancedrug targets |
| spellingShingle | Ahmed Seddek Thirunavukkarasu Annamalai Yuk-Ching Tse-Dinh Type IA Topoisomerases as Targets for Infectious Disease Treatments Microorganisms topoisomerase antimicrobial resistance drug targets |
| title | Type IA Topoisomerases as Targets for Infectious Disease Treatments |
| title_full | Type IA Topoisomerases as Targets for Infectious Disease Treatments |
| title_fullStr | Type IA Topoisomerases as Targets for Infectious Disease Treatments |
| title_full_unstemmed | Type IA Topoisomerases as Targets for Infectious Disease Treatments |
| title_short | Type IA Topoisomerases as Targets for Infectious Disease Treatments |
| title_sort | type ia topoisomerases as targets for infectious disease treatments |
| topic | topoisomerase antimicrobial resistance drug targets |
| url | https://www.mdpi.com/2076-2607/9/1/86 |
| work_keys_str_mv | AT ahmedseddek typeiatopoisomerasesastargetsforinfectiousdiseasetreatments AT thirunavukkarasuannamalai typeiatopoisomerasesastargetsforinfectiousdiseasetreatments AT yukchingtsedinh typeiatopoisomerasesastargetsforinfectiousdiseasetreatments |