Abstract

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.

Highlights

  • We analyzed the dose-response curves of the clomiphene citrate (CC) for response curves of the CC for M. abscessus in Mueller-Hinton broth (MH) and 7H9 broth

  • These results suggest CC is an attractive substance for all kinds of anti-M. abscessus therapy

  • Non-tuberculosis mycobacteria (NTM) infections are more common than tuberculosis in industrialized countries, and cases are likely to increase about diseases caused by NTM, especially infections are moreglobally

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Non-tuberculosis mycobacteria (NTM) are highly abundant in environmental niches such as soil and water sources, often leading to high human-pathogen contact [1]. Several host factors, such as the ageing of the global population, lung diseases including cystic fibrosis (CF) and bronchiectasis, immunosuppressive, and broad-spectrum antibiotic therapy, contribute to the rise of NTM infections. NTM infections regularly surpass the global incidence of new tuberculosis infections in developed countries [1]

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