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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Published in:Pharmaceutics 2022-03, Vol.14 (3), p.552
Main Authors: Cho, Hyejin, Kim, Kwang-Sun
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Antibiotics
Bacteria
Bacterial infections
Cancer
Cell division
ciclopirox
Digital cameras
drug repurposing
Drug resistance
E coli
Experiments
Genes
Gram-negative bacteria
Infections
Kinases
motility
multidrug-resistant
Salmonella
zidovudine (azidothymidine)
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Summary: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 , whereas AZT displayed no selectivity for any antibiotic-resistant strain. Motility assays revealed that β-lactamase-producing strains were less motile in nature and more strongly affected by CPX than a parental strain. Resistance against CPX was not observed in 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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14030552