Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms222011029
Keywords
Mycobacterium abscessus; clomiphene citrate; drug repurposing; drug resistance; non-tuberculosis mycobacteria
Funding
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI20C0478]
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The study identified the drug clomiphene citrate (CC) as a potential treatment for M. abscessus infections, inhibiting the growth of both wild-type strains and resistant strains, as well as showing efficacy against biofilm. CC did not exhibit cytotoxicity in infected cells, suggesting its potential as a new drug therapy for M. abscessus infections.
Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections and is the most difficult non-tuberculous mycobacteria (NTM) to treat due to its resistance to current antimicrobial drugs, with a treatment success rate of 45.6%. Thus, novel treatment drugs are needed, of which we identified the drug clomiphene citrate (CC), known to treat infertility in women, to exhibit inhibitory activity against M. abscessus. To assess the potential of CC as a treatment for M. abscessus pulmonary diseases, we measured its efficacy in vitro and established the intracellular activity of CC against M. abscessus in human macrophages. CC significantly inhibited the growth of not only wild-type M. abscessus strains but also clinical isolate strains and clarithromycin (CLR)-resistant strains of M. abscessus. CC's drug efficacy did not have cytotoxicity in the infected macrophages. Furthermore, CC worked in anaerobic non-replicating conditions as well as in the presence of biofilm. The results of this in vitro study on M. abscessus activity suggest the possibility of using CC to develop new drug hypotheses for the treatment of M. abscessus infections.
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