High rate of mobilization for blaCTX-Ms

Abstract

We constructed a phylogenetic analysis of class A beta-lactamases and found that the blaCTX-Ms have been mobilized to plasmids approximately 10 times more frequently than other class A beta-lactamases. We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer. Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted. That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

Figure 1

Phylogenetic analysis of bla_CTX-Ms. This tree was calculated by Bayesian inference. Number of mutations occurring along each branch are given along the length of the branch. Black dots represent mobilizations. Boldface indicates chromosomal genes. CTX-M-14 and 3a exist as both unmobilized chromosomal genes and plasmid-borne CTX-M alleles.

Figure 2

Phylogenetic analysis of class A β-lactamases calculated by Bayesian inference. Number of mutations occurring along each branch are represented visually by the lengths of the branches. d_N /dS ratios for all branches except the tips are given along the lengths of the branches. Boldface indicates plasmidic genes. Black dots indicate mobilizations to plasmids. Numbered brackets indicate monophyletic divisions within the tree. *d_N, nonsynonymous substitution rate; d_S, synonoymous substitution rate.