Class D β-lactamases do exist in Gram-positive bacteria.

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Bacterial resistance to beta-lactam antibiotics is a major global health concern.
• Beta-lactamases, particularly class D enzymes, are key mediators of this resistance, primarily identified in Gram-negative bacteria.
• The absence of reported class D beta-lactamases in Gram-positive bacteria represented a knowledge gap.

Purpose of the Study:

• To investigate the presence and characteristics of class D beta-lactamases in Gram-positive bacteria.
• To determine if these enzymes exhibit broad substrate hydrolysis capabilities.
• To understand the structural and functional novelty of these enzymes compared to known beta-lactamases.

Main Methods:

• Genomic analysis of environmental Gram-positive bacteria.
• Enzyme activity assays using various beta-lactam substrates.
• Structural analysis and comparison with known beta-lactamase classes.

Main Results:

• Efficient class D beta-lactamases were found to be widespread in diverse Gram-positive species.
• These novel enzymes effectively hydrolyze a broad spectrum of beta-lactam antibiotics.
• Gram-positive class D beta-lactamases possess unique structural features and substrate-binding modes.

Conclusions:

• Class D beta-lactamases are not exclusive to Gram-negative pathogens and are prevalent in environmental Gram-positive bacteria.
• These enzymes represent a significant, previously unrecognized source of antibiotic resistance.
• Their distinct architecture and function offer new insights into beta-lactamase evolution and substrate interaction.