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2-Aminoimidazoles Inhibit Mycobacterium abscessus Biofilms in a Zinc-Dependent Manner

Biofilm growth is thought to be a significant obstacle to the successful treatment of Mycobacterium abscessus infections. A search for agents capable of inhibiting M. abscessus biofilms led to our interest in 2-aminoimidazoles and related scaffolds, which have proven to display antibiofilm propertie...

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Detalles Bibliográficos
Autores principales: Belardinelli, Juan M., Li, Wei, Martin, Kevin H., Zeiler, Michael J., Lian, Elena, Avanzi, Charlotte, Wiersma, Crystal J., Nguyen, Tuan Vu, Angala, Bhanupriya, de Moura, Vinicius C. N., Jones, Victoria, Borlee, Bradley R., Melander, Christian, Jackson, Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951752/
https://www.ncbi.nlm.nih.gov/pubmed/35328372
http://dx.doi.org/10.3390/ijms23062950
Descripción
Sumario:Biofilm growth is thought to be a significant obstacle to the successful treatment of Mycobacterium abscessus infections. A search for agents capable of inhibiting M. abscessus biofilms led to our interest in 2-aminoimidazoles and related scaffolds, which have proven to display antibiofilm properties against a number of Gram-negative and Gram-positive bacteria, including Mycobacterium tuberculosis and Mycobacterium smegmatis. The screening of a library of 30 compounds led to the identification of a compound, AB-2-29, which inhibits the formation of M. abscessus biofilms with an IC(50) (the concentration required to inhibit 50% of biofilm formation) in the range of 12.5 to 25 μM. Interestingly, AB-2-29 appears to chelate zinc, and its antibiofilm activity is potentiated by the addition of zinc to the culture medium. Preliminary mechanistic studies indicate that AB-2-29 acts through a distinct mechanism from those reported to date for 2-aminoimidazole compounds.