2-Aminoimidazoles Inhibit <i>Mycobacterium abscessus</i> Biofilms in a Zinc-Dependent Manner
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 p...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/6/2950 |
| Summary: | 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 led to the identification of a compound, AB-2-29, which inhibits the formation of <i>M. abscessus</i> biofilms with an IC<sub>50</sub> (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. |
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| ISSN: | 1661-6596 1422-0067 |