IMP-27, a Unique Metallo-β-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis

Area of Science:

• Microbiology
• Molecular Biology
• Antimicrobial Resistance

Background:

• Metallo-β-lactamases (MBLs) are a significant threat in antimicrobial resistance.
• Integrons, particularly class 2 integrons, are mobile genetic elements that facilitate the spread of resistance genes.
• Proteus mirabilis is an opportunistic pathogen known to acquire resistance mechanisms.

Purpose of the Study:

• To identify and characterize a novel metallo-β-lactamase gene in Proteus mirabilis.
• To investigate the genetic context and location of the novel gene within mobile genetic elements.
• To evaluate the phenotypic and enzymatic activity of the identified metallo-β-lactamase.

Main Methods:

• Whole-genome sequencing of Proteus mirabilis isolates.
• Antimicrobial susceptibility testing (AST) using standard methods.
• Gene cloning and expression of the novel metallo-β-lactamase.
• Enzyme activity assays (hydrolysis assays) with various β-lactam antibiotics.

Main Results:

• Identification of a novel metallo-β-lactamase gene, designated blaIMP-27, in unrelated Proteus mirabilis isolates from different US locations.
• The blaIMP-27 gene was found within a class 2 integron, suggesting potential for horizontal gene transfer.
• Antimicrobial susceptibility testing showed resistance to ertapenem but susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime.
• Hydrolysis assays confirmed that the IMP-27 enzyme efficiently hydrolyzes ceftazidime, explaining the discrepancy between AST and enzymatic activity.

Conclusions:

• The blaIMP-27 gene represents a new MBL variant identified in Proteus mirabilis.
• Its presence in a class 2 integron highlights the role of these elements in disseminating novel resistance genes.
• The enzymatic activity of IMP-27 against ceftazidime necessitates careful interpretation of susceptibility testing and has implications for treatment strategies.