Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria
Multidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral ant...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/552 |
| _version_ | 1827626611067846656 |
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| author | Hyejin Cho Kwang-sun Kim |
| author_facet | Hyejin Cho Kwang-sun Kim |
| author_sort | Hyejin Cho |
| collection | DOAJ |
| description | Multidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral antiviral agent, is a leading repurposed drug against MDR Gram-negative bacterial infections. However, the rapid emergence of bacterial resistance due to long-term exposure, overuse, or misuse limits its application, making it necessary to develop new alternatives. In this study, we investigated the efficacy of ciclopirox (CPX) as an alternative to AZT. The minimum inhibitory concentrations of AZT and CPX against MDR Gram-negative bacteria were determined; CPX appeared more active against β-lactamase-producing <i>Escherichia coli</i>, whereas AZT displayed no selectivity for any antibiotic-resistant strain. Motility assays revealed that β-lactamase-producing <i>Escherichia coli</i> strains were less motile in nature and more strongly affected by CPX than a parental strain. Resistance against CPX was not observed in <i>E. coli</i> even after 25 days of growth, whereas AZT resistance was observed in less than 2 days. Moreover, CPX effectively killed AZT-resistant strains with different resistance mechanisms. Our findings indicate that CPX may be utilized as an alternative or supplement to AZT-based medications to treat opportunistic Gram-negative bacterial infections. |
| first_indexed | 2024-03-09T12:59:19Z |
| format | Article |
| id | doaj.art-ec4da9cf170f4574b99adb997c6ec49d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:59:19Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ec4da9cf170f4574b99adb997c6ec49d2023-11-30T21:56:30ZengMDPI AGPharmaceutics1999-49232022-03-0114355210.3390/pharmaceutics14030552Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative BacteriaHyejin Cho0Kwang-sun Kim1Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, KoreaDepartment of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, KoreaMultidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral antiviral agent, is a leading repurposed drug against MDR Gram-negative bacterial infections. However, the rapid emergence of bacterial resistance due to long-term exposure, overuse, or misuse limits its application, making it necessary to develop new alternatives. In this study, we investigated the efficacy of ciclopirox (CPX) as an alternative to AZT. The minimum inhibitory concentrations of AZT and CPX against MDR Gram-negative bacteria were determined; CPX appeared more active against β-lactamase-producing <i>Escherichia coli</i>, whereas AZT displayed no selectivity for any antibiotic-resistant strain. Motility assays revealed that β-lactamase-producing <i>Escherichia coli</i> strains were less motile in nature and more strongly affected by CPX than a parental strain. Resistance against CPX was not observed in <i>E. coli</i> even after 25 days of growth, whereas AZT resistance was observed in less than 2 days. Moreover, CPX effectively killed AZT-resistant strains with different resistance mechanisms. Our findings indicate that CPX may be utilized as an alternative or supplement to AZT-based medications to treat opportunistic Gram-negative bacterial infections.https://www.mdpi.com/1999-4923/14/3/552ciclopiroxdrug repurposingzidovudine (azidothymidine)multidrug-resistantmotility |
| spellingShingle | Hyejin Cho Kwang-sun Kim Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria Pharmaceutics ciclopirox drug repurposing zidovudine (azidothymidine) multidrug-resistant motility |
| title | Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria |
| title_full | Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria |
| title_fullStr | Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria |
| title_full_unstemmed | Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria |
| title_short | Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria |
| title_sort | repurposing of ciclopirox to overcome the limitations of zidovudine azidothymidine against multidrug resistant gram negative bacteria |
| topic | ciclopirox drug repurposing zidovudine (azidothymidine) multidrug-resistant motility |
| url | https://www.mdpi.com/1999-4923/14/3/552 |
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