Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria.
Tuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0213713 |
| _version_ | 1798032111819554816 |
|---|---|
| author | Panchali Kanvatirth Rose E Jeeves Joanna Bacon Gurdyal S Besra Luke J Alderwick |
| author_facet | Panchali Kanvatirth Rose E Jeeves Joanna Bacon Gurdyal S Besra Luke J Alderwick |
| author_sort | Panchali Kanvatirth |
| collection | DOAJ |
| description | Tuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this deadly disease. The current TB drug regimen is inadequate, takes months to complete and poses significant challenges when administering to patients suffering from drug resistant TB. New treatments that are faster, simpler and more affordable are urgently required. Arguably, a good strategy to discover new drugs is to start with an old drug. Here, we have screened a library of 1200 FDA approved drugs from the Prestwick Chemical library using a GFP microplate assay. Drugs were screened against GFP expressing strains of Mycobacterium smegmatis and Mycobacterium bovis BCG as surrogates for Mycobacterium tuberculosis, the causative agent of TB in humans. We identified several classes of drugs that displayed antimycobacterial activity against both M. smegmatis and BCG, however each organism also displayed some selectivity towards certain drug classes. Variant analysis of whole genomes sequenced for resistant mutants raised to florfenicol, vanoxerine and pentamidine highlight new pathways that could be exploited in drug repurposing programmes. |
| first_indexed | 2024-04-11T20:07:33Z |
| format | Article |
| id | doaj.art-e3177294040b4e42b8c051f238a6a6ed |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T20:07:33Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e3177294040b4e42b8c051f238a6a6ed2022-12-22T04:05:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021371310.1371/journal.pone.0213713Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria.Panchali KanvatirthRose E JeevesJoanna BaconGurdyal S BesraLuke J AlderwickTuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this deadly disease. The current TB drug regimen is inadequate, takes months to complete and poses significant challenges when administering to patients suffering from drug resistant TB. New treatments that are faster, simpler and more affordable are urgently required. Arguably, a good strategy to discover new drugs is to start with an old drug. Here, we have screened a library of 1200 FDA approved drugs from the Prestwick Chemical library using a GFP microplate assay. Drugs were screened against GFP expressing strains of Mycobacterium smegmatis and Mycobacterium bovis BCG as surrogates for Mycobacterium tuberculosis, the causative agent of TB in humans. We identified several classes of drugs that displayed antimycobacterial activity against both M. smegmatis and BCG, however each organism also displayed some selectivity towards certain drug classes. Variant analysis of whole genomes sequenced for resistant mutants raised to florfenicol, vanoxerine and pentamidine highlight new pathways that could be exploited in drug repurposing programmes.https://doi.org/10.1371/journal.pone.0213713 |
| spellingShingle | Panchali Kanvatirth Rose E Jeeves Joanna Bacon Gurdyal S Besra Luke J Alderwick Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. PLoS ONE |
| title | Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. |
| title_full | Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. |
| title_fullStr | Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. |
| title_full_unstemmed | Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. |
| title_short | Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria. |
| title_sort | utilisation of the prestwick chemical library to identify drugs that inhibit the growth of mycobacteria |
| url | https://doi.org/10.1371/journal.pone.0213713 |
| work_keys_str_mv | AT panchalikanvatirth utilisationoftheprestwickchemicallibrarytoidentifydrugsthatinhibitthegrowthofmycobacteria AT roseejeeves utilisationoftheprestwickchemicallibrarytoidentifydrugsthatinhibitthegrowthofmycobacteria AT joannabacon utilisationoftheprestwickchemicallibrarytoidentifydrugsthatinhibitthegrowthofmycobacteria AT gurdyalsbesra utilisationoftheprestwickchemicallibrarytoidentifydrugsthatinhibitthegrowthofmycobacteria AT lukejalderwick utilisationoftheprestwickchemicallibrarytoidentifydrugsthatinhibitthegrowthofmycobacteria |