Phylogenetic Tree and Sequence Similarity of β-Lactamases

Abstract

β-Lactamases are the main cause of β-lactam resistance in many pathogenic bacteria. These enzymes can be detected in a variety of pathogenic as well as non-pathogenic bacteria. The cyanobacteria are also known to produce a β-lactamase. Recently, the amino acid sequences and the three-dimensional structures of some of these β-lactamases have been clarified. On the basis of the amino acid sequences of 47 β-lactamases and the computer-aided analysis, a phylogenetic tree is proposed in this paper. According to the tree, β-lactamases are classified into six groups. Group 1 β-lactamases are mainly composed of plasmid-mediated enzymes from gram-negative bacteria. However, chromosome-derived β-lactamases from Klebsiella pneumoniae and Rhodopseudomonas capsulata take part in this group. Group 2 enzymes consist of a part of the chromosome-encoded β-lactamases from Streptomyces, and chromosome-mediated enzymes from Yersinia enterocolitica, Citrobacter diversus, and Klebsiella oxytoca. Chromosome-encoded β-lactamases from gram-negative bacteria form group 3. Group 4 is composed of metalloenzymes, whereas group 5 consists of OXA type β-lactamases. Chromosome-encoded β-lactamases from gram-positive bacteria form group 6. Comparison of the amino acid sequences among these groups confirmed the phylogenetic tree and the classification: the β-lactamases in each group have its particular conserved amino acid sequences. In addition, the tree provides more detailed classification and time-scale mutual relationships and predicts new types of β-lactamases that may be found. Furthermore, the classification deduced from the tree is generally in accord with the one based on the amino acid sequences reported previously. However, the class A β-lactamases are clearly divided into three groups: groups 1, 2, and 6. RDF2 analysis shows that some combinations between β-lactamases and β-lactam-interacting proteins as well as eukaryotic proteins have a low but significant evolutionary relatedness.