A Novel Metallo‐β‐Lactamase AMM‐1 From Alteromonas mangrovi Reveals a Cryptic Environmental Reservoir of Carbapenem Resistance
ABSTRACT Carbapenem resistance driven by metallo‐β‐lactamases (MBLs) poses a formidable global challenge as these enzymes can degrade a wide range of β‐lactam antibiotics, including last‐line carbapenems. Despite extensive documentation of MBL‐producing pathogens, their evolutionary origins and ecol...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
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| Series: | Microbial Biotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1751-7915.70191 |
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| Summary: | ABSTRACT Carbapenem resistance driven by metallo‐β‐lactamases (MBLs) poses a formidable global challenge as these enzymes can degrade a wide range of β‐lactam antibiotics, including last‐line carbapenems. Despite extensive documentation of MBL‐producing pathogens, their evolutionary origins and ecological reservoirs are still poorly understood. Here, we report the discovery and in‐depth characterisation of AMM‐1, a previously unrecognised B1.2 MBL identified within a metagenome‐assembled genome of Alteromonas mangrovi obtained from the Yangtze River Estuary. Comparative sequence analyses and phylogenetics reveal that AMM‐1 clusters closely with clinically significant MBLs, underscoring its potential impact to human health. Structural modelling confirms the presence of a conserved di‐zinc binding site critical for β‐lactam hydrolysis, while heterologous expression in Escherichia coli (E. coli) demonstrates a marked increase in resistance against multiple β‐lactam classes, including carbapenems. Phylogenetic depth analysis and ancestral reconstruction delineate AMM‐1's distinct evolutionary path, placing it deeper than IMP‐1 and SPM‐1 but shallower than NDM‐1. Flexibility simulations reveal unique active‐site loop dynamics (L3 and L10), with reduced mobility in key regions that shape substrate binding stability and spectrum. Notably, AMM‐1 is stably located on the host chromosome without flanking mobile genetic elements, suggesting that it may have persisted as a vertically inherited trait rather than a recently acquired component of a mobile resistome. These findings highlight the capacity of environmental microbes to serve as long‐standing, cryptic reservoirs of potent resistance determinants, emphasising the need for integrated environmental surveillance and preemptive stewardship strategies. By unveiling the molecular and functional properties of AMM‐1, this work provides critical insights into how resistance elements can reside, evolve and potentially mobilise within natural habitats, ultimately informing efforts to predict and mitigate the future emergence of carbapenem‐resistant bacterial pathogens. |
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| ISSN: | 1751-7915 |