Repurposing thioridazine as a potential CD2068 inhibitor to mitigate antibiotic resistance in Clostridioides difficile infection
3
Issued Date
2025-01-01
Resource Type
eISSN
20010370
Scopus ID
2-s2.0-85219372604
Journal Title
Computational and Structural Biotechnology Journal
Volume
27
Start Page
887
End Page
895
Rights Holder(s)
SCOPUS
Bibliographic Citation
Computational and Structural Biotechnology Journal Vol.27 (2025) , 887-895
Suggested Citation
Pipatthana M., Phanchana M., Sangphukieo A., Charoensutthivarakul S., Harnvoravongchai P., Chankhamhaengdecha S., Prangthip P., Konpetch P., Sripong C., Wongphayak S., Janvilisri T. Repurposing thioridazine as a potential CD2068 inhibitor to mitigate antibiotic resistance in Clostridioides difficile infection. Computational and Structural Biotechnology Journal Vol.27 (2025) , 887-895. 895. doi:10.1016/j.csbj.2025.02.036 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/105609
Title
Repurposing thioridazine as a potential CD2068 inhibitor to mitigate antibiotic resistance in Clostridioides difficile infection
Corresponding Author(s)
Other Contributor(s)
Abstract
Clostridioides difficile infection (CDI) is a major public health issue, driven by antibiotic resistance and frequent recurrence. CD2068, an ABC protein in C. difficile, is associated with drug resistance, making it a potential target for novel therapies. This study explored FDA-approved non-antibiotic drugs for their ability to inhibit CD2068 through drug screening and experimental validation. Thioridazine exhibited moderate binding affinity to CD2068 and inhibited its ATP hydrolysis activity. It also suppressed the growth of multiple C. difficile ribotypes at 64–128 µg/mL, with rapid-killing effects. When combined with sub-MIC levels of standard antibiotics, thioridazine significantly reduced bacterial growth. In a mouse CDI model, thioridazine demonstrated potential in restoring gut microbial balance and improving survival, although it did not show superiority to vancomycin. These findings suggest that thioridazine has potential as a novel therapeutic for CDI, either as an adjunct to existing antibiotics or as part of a combination therapy to combat antibiotic resistance. Further research, including replication studies and dose optimization, is needed to fully evaluate thioridazine's therapeutic potential.