Phylogenetic tree and sequence similarity of beta-lactamases.

beta-Lactamases are the main cause of beta-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 beta-lactamase. Recently, the amino acid sequences and the three-dimensional structures of some of these beta-lactamases have been clarified. On the basis of the amino acid sequences of 47 beta-lactamases and the computer-aided analysis, a phylogenetic tree is proposed in this paper. According to the tree, beta-lactamases are classified into six groups. Group 1 beta-lactamases are mainly composed of plasmid-mediated enzymes from gram-negative bacteria. However, chromosome-derived beta-lactamases from Klebsiella pneumoniae and Rhodopseudomonas capsulata take part in this group. Group 2 enzymes consist of a part of the chromosome-encoded beta-lactamases from Streptomyces, and chromosome-mediated enzymes from Yersinia enterocolitica, Citrobacter diversus, and Klebsiella oxytoca. Chromosome-encoded beta-lactamases from gram-negative bacteria form group 3. Group 4 is composed of metalloenzymes, whereas group 5 consists of OXA type beta-lactamases. Chromosome-encoded beta-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 beta-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 beta-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 beta-lactamases are clearly divided into three groups: groups 1, 2, and 6. RDF2 analysis shows that some combinations between beta-lactamases and beta-lactam-interacting proteins as well as eukaryotic proteins have a low but significant evolutionary relatedness.