Identification of a Drug Candidate against <i>Mycobacterium avium</i> Using Pandemic Response Box

MAC (<i>Mycobacterium avium</i> complex) is a naturally occurring environmental microorganism found worldwide in sources such as soil and water. Among nontuberculous mycobacteria (NTM), MAC is the species most commonly responsible for pulmonary infections, particularly in immunocompromised individuals. In addition to pulmonary disease, extrapulmonary <i>M. avium</i> infections can present as disseminated, cutaneous, or lymphatic diseases. Skin infections caused by <i>M. avium</i> can vary significantly between patients, with both localized and disseminated forms observed. Despite the increasing prevalence of extrapulmonary NTM infections, treatment outcomes remain suboptimal, underscoring the need for novel therapeutic strategies. In this study, we conducted in vitro dual-screening using the Pandemic Response Box against <i>M. avium</i> 104, and identified alexidine (AX) as a promising candidate for therapy. Further evaluation demonstrated that chlorhexidine (CHX), a structurally distinct bis-biguanide compound, also exhibited potent inhibitory activity against <i>M. avium</i> growth in vitro, as well as in a zebrafish model of <i>M. avium</i> infection and treatment. These findings suggest that CHX may be a potential therapeutic candidate for treating <i>M. avium</i> skin infections.