Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection

Abstract

<i>Mycobacterium abscessus</i> is a rapid-growing, multidrug-resistant, non-tuberculous mycobacterial species responsible for a variety of human infections, such as cutaneous and pulmonary infections. <i>M. abscessus</i> infections are very difficult to eradicate due to the natural and acquired multidrug resistance profiles of <i>M. abscessus</i>. Thus, there is an urgent need for the development of effective drugs or regimens against <i>M. abscessus</i> infections. Here, we report the activity of a US Food and Drug Administration approved drug, thiostrepton, against <i>M. abscessus</i>. We found that thiostrepton significantly inhibited the growth of <i>M. abscessus</i> wild-type strains, subspecies, clinical isolates, and drug-resistant mutants in vitro and in macrophages. In addition, treatment of macrophages with thiostrepton significantly decreased proinflammatory cytokine production in a dose-dependent manner, suggesting an inhibitory effect of thiostrepton on inflammation induced during <i>M. abscessus</i> infection. We further showed that thiostrepton exhibits antimicrobial effects in vivo using a zebrafish model of <i>M. abscessus</i> infection.