Evolutionary origin of the class A and class C beta-lactamases

Area of Science:

• Microbiology
• Evolutionary Biology
• Biochemistry

Background:

• Beta-lactamases are enzymes that confer bacterial resistance to beta-lactam antibiotics.
• Class A and Class C beta-lactamases are significant in clinical settings due to their role in antibiotic resistance.
• Understanding the evolutionary origins of these enzymes is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the evolutionary origins and diversification of class A and class C beta-lactamases.
• To determine the ancestral relationship between beta-lactamases and other related enzymes.
• To elucidate the transmission pathways of class A beta-lactamases among bacterial species.

Main Methods:

• Phylogenetic analysis of protein sequences from class A and class C beta-lactamases.
• Construction of a rooted phylogenetic tree using DD peptidase as an outgroup.
• Comparative analysis of beta-lactamase genes within Streptomyces and non-actinomycete bacteria.

Main Results:

• Penicillin-binding proteins are identified as the most probable ancestral origin of class A and C beta-lactamases.
• Actinomycetes are confirmed as the origin of class A beta-lactamases found in non-actinomycete species.
• Evidence suggests horizontal gene transfer facilitated the spread of class A beta-lactamases from Streptomyces to other bacteria, including gram-positive and gram-negative species, and within Streptomyces itself.

Conclusions:

• The evolutionary trajectory of beta-lactamases points to penicillin-binding proteins as ancestral.
• Streptomyces species played a pivotal role in the origin and dissemination of class A beta-lactamases.
• Horizontal gene transfer is a significant mechanism driving the evolution and spread of antibiotic resistance genes.