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

Autor: Juan M. Belardinelli, Wei Li, Kevin H. Martin, Michael J. Zeiler, Elena Lian, Charlotte Avanzi, Crystal J. Wiersma, Tuan Vu Nguyen, Bhanupriya Angala, Vinicius C. N. de Moura, Victoria Jones, Bradley R. Borlee, Christian Melander, Mary Jackson
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 23; Issue 6; Pages: 2950
ISSN: 1661-6596
DOI: 10.3390/ijms23062950
Popis: Biofilm growth is thought to be a significant obstacle to the successful treatment ofMycobacterium abscessusinfections. A search for agents capable of inhibitingM. abscessusbiofilms 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, includingMycobacterium tuberculosisandMycobacterium smegmatis. The screening of a library of 30 compounds led to the identification of a compound, AB-2-29, which inhibits the formation ofM. abscessusbiofilms with an IC50(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.
Databáze: OpenAIRE
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