Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but...

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Bacterial β-lactamase enzymes hydrolyze β-lactam antibiotics, conferring resistance.
• Antibiotic overuse drives rapid evolution of β-lactamase resistance activities.
• Global physiochemical properties of β-lactamases show both conservation and variability.

Purpose of the Study:

• To characterize property conservation within class-A β-lactamases.
• To establish if physiochemical variations correlate with evolutionary history.
• To investigate the link between enzyme properties, phylogeny, and environmental conditions.

Main Methods:

• Analysis of twelve class-A β-lactamase enzymes.
• Characterization of global physiochemical properties, including electrostatic potential maps, residue-to-residue couplings, pKa values, electrostatic networks, and backbone flexibility.
• Statistical analysis to correlate properties with phylogenetic data and bacterial environmental conditions.

Main Results:

• Systematic variations in electrostatic potential maps and residue couplings reflect phylogenetic relationships.
• Conserved properties like pKa values and backbone flexibility also show statistically significant variations that parallel phylogeny.
• Enzyme properties correlate significantly with the environmental conditions of their host bacteria.
• Antibiotic resistance activities did not significantly constrain global physiochemical properties.

Conclusions:

• Systematic variations in β-lactamase physiochemical properties mirror their evolutionary trajectory.
• Environmental conditions, not functional specificity, significantly shape these global properties.
• Extended-spectrum antibiotic resistance can emerge across diverse physiochemical backgrounds.