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


ABSTRACT: 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 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.

SUBMITTER: Belardinelli JM 

PROVIDER: S-EPMC8951752 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Biofilm growth is thought to be a significant obstacle to the successful treatment of <i>Mycobacterium abscessus</i> infections. A search for agents capable of inhibiting <i>M. abscessus</i> 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 <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium smegmatis</i>. The screening of a library of 30 compounds  ...[more]

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