Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection

Kim, Tae Ho; Hanh, Bui Thi Bich; Kim, Guehye; Lee, Da-Gyum; Park, June-Woo; Lee, So Eui; Kim, Jae-Sung; Kim, Byoung Soo; Ryoo, Sungweon; Jo, Eun-Kyeong; Jang, Jichan

doi:10.3390/molecules24244511

Cited by 26 publications

(26 citation statements)

References 45 publications

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“…Therefore, etamycin can be considered an effective drug candidate for drug-resistant strains. [11]. As shown in Figure 2b…”

Section: Etamycin Exhibits Potent Activity Against M Abscesuss Subspmentioning

confidence: 72%

“…Lastly, this therapeutic activity was also confirmed in vivo using zebrafish (ZF). ZF is a popular animal model for in vivo antitubercular drug discovery [11,15,22,26]. In particular, this model is a very good tractable model for M. abscessus and M. marinum that can survive and replicate at cold environments (~30 • C).…”

Section: Discussionmentioning

confidence: 99%

“…To determine the therapeutic potential of etamycin, the drug in vivo efficacy was evaluated in zebrafish after infection with mWasabi protein-expressing M. abscessus, as described previously [11]. As M. abscessus CIP 104536 T (R) is hypervirulent in animal models, we evaluated the activity of etamycin against M. abscessus CIP 104536 T (R) at concentrations of 10, 25, and 50 µM [12].…”

Section: Etamycin Shows Antimicrobial Activity Against Rough Morphotymentioning

confidence: 99%

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Etamycin as a Novel Mycobacterium abscessus Inhibitor

Hanh

Kim

Park

et al. 2020

IJMS

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The increase in drug-resistant Mycobacterium abscessus, which has become resistant to existing standard-of-care agents, is a major concern, and new antibacterial agents are strongly needed. In this study, we introduced etamycin that showed an excellent activity against M. abscessus. We found that etamycin significantly inhibited the growth of M. abscessus wild-type strain, three subspecies, and clinical isolates in vitro and inhibited the growth of M. abscessus that resides in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of etamycin in the zebrafish (Danio rerio) infection model was greater than that of clarithromycin, which is recommended as the core agent for treating M. abscessus infections. Thus, we concluded that etamycin is a potential anti-M. abscessus candidate for further development as a clinical drug candidate.

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“…Therefore, etamycin can be considered an effective drug candidate for drug-resistant strains. [11]. As shown in Figure 2b…”

Section: Etamycin Exhibits Potent Activity Against M Abscesuss Subspmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Etamycin Shows Antimicrobial Activity Against Rough Morphotymentioning

confidence: 99%

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Etamycin as a Novel Mycobacterium abscessus Inhibitor

Hanh

Kim

Park

et al. 2020

IJMS

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“…Reagents and media compositions were purchased from Sigma-Aldrich (St. Louis, MO, USA). Recombinant M. abscessus CIP 104536 T R morphotype carrying a pMV262-GFP plasmid that express green fluorescent protein (GFP) was prepared as previously described [21]. To prepare fresh injection stock, M. abscessus (∼5 × 10 5 colony-forming unit (CFU)) expressing GFP was harvested by centrifugation at 4000× g for 5 min, and the pellet was washed twice using 100 µL of 7H9 G/T/ADC .…”

Section: Bacterial Strains and Growing Conditionsmentioning

confidence: 99%

“…4.6. Drug Efficacy Assessment in M. Abscessus-infected ZF and the Use of Ziehl-Neelsen Staining Dechorionated and anesthetized ZF embryos at 30 to 48 h post-fertilization (hpf) were injected with 3 nL of titrated M. abscessus expressing GFP frozen stock containing~400 CFU into the caudal vein using a Nanoject III microinjector (Drummond Scientific, Broomall, PA, USA) as previously described [21]. The infection size (3 nL) was enumerated on 7H10 T/OADC supplemented with 50 µg/mL kanamycin.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent

et al. 2020

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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.

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Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

Egorova¹,

Jackson

Gavrilyuk³

et al. 2021

Medicinal Research Reviews

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The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti‐M. abscessus small‐molecule drug development process can be enhanced by two parallel strategies—discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small‐molecule agents, and more particularly focuses on the activity, mode of action and structure–activity relationship of promising inhibitors from five different chemical classes—benzimidazoles, indole‐2‐carboxamides, benzothiazoles, 4‐piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessus that may be worthy of future drug and adjunct therapeutic development.

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Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection

Cited by 26 publications

References 45 publications

Etamycin as a Novel Mycobacterium abscessus Inhibitor

Etamycin as a Novel Mycobacterium abscessus Inhibitor

Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

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