Abstract
Mycobacterium abscessus is the most difficult-to-treat nontuberculous mycobacteria because of its resistance to many antibiotics. In this study, we screened the Korea Chemical Bank library for a bioluminescent reporter assay to identify molecules capable of acting against M. abscessus. On application of the assay, rifamycin O showed excellent in vitro activity with a narrow range of the minimum inhibitory concentration required to inhibit the growth of 90% of the bacterium (MIC90 = 4.0–6.2 μM); its in vivo efficacy in the zebrafish (Danio rerio) infection model was comparable to that of rifabutin at 25 μM. Furthermore, rifamycin O did not show significant toxicity in cells and the zebrafish model. These results are the first in vivo indication that rifamycin O may be a drug candidate for treating M. abscessus infections.
Highlights
Mycobacterium abscessus is a rapidly growing saprophyte, commonly found in soil and water [1].M. abscessus is known to cause chronic lung and skin infections in immunocompromised hosts, which are difficult to treat due to antimicrobial drug resistance [2]
Based on the findings reported by Rominski et al, the genetic approach with the Arr enzyme of M. abscessus (Arr_Mab)-deletion mutant showed much lower minimum inhibitory concentration (MIC) values than the parental strain, and its compensated strain restored the wild type phenotype against rifamycin [8]
This study aimed to search for alternative compounds for treatment of M. abscessus infections by screening all available compounds deposited in the Korea Chemical Bank (KCB) library
Summary
Mycobacterium abscessus is a rapidly growing saprophyte, commonly found in soil and water [1]. M. abscessus is known to cause chronic lung and skin infections in immunocompromised hosts, which are difficult to treat due to antimicrobial drug resistance [2]. In order to treat the infections caused by. M. abscessus, a multi-drug cocktail comprising clarithromycin, amikacin, and cefoxitin or imipenem has been used [3]. Clarithromycin is known to be the most effective drug used to treat M. abscessus [3]. There is still a high rate of treatment failures (20%–73%) because M. abscessus has both natural and acquired drug resistance to clarithromycin [4]. Based on whole-genome studies, M. abscessus comprises three different subspecies: M. abscessus subsp. Based on whole-genome studies, M. abscessus comprises three different subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp
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