Origin and evolution of the AmpC beta-lactamases of Citrobacter freundii

Abstract

To determine whether the widespread clinical use of beta-lactams has been selective for Citrobacter freundii-derived alleles of plasmid ampC genes, we generated a Bayesian consensus phylogeny of the published ampC sequences and compared the MICs of 16 beta-lactam antibiotics for Escherichia coli strains containing cloned copies of the C. freundii ampC alleles. We found that for the majority of compounds investigated, there has been essentially no increase in beta-lactam resistance conferred by those alleles. We also found that ampC alleles from the chromosomes of two beta-lactam-sensitive C. freundii strains isolated in the 1920s, before the clinical use of antibiotics, were as effective at providing beta-lactam resistance in E. coli as were the plasmid-borne alleles from beta-lactam-resistant clinical isolates. These results suggest that selection for increased resistance to beta-lactam antibiotics has not been a significant force directing the evolution of the C. freundii ampC alleles found in beta-lactam-resistant clinical isolates.

FIG. 1.

Bayesian consensus phylogeny of the ampC genes. Probabilities of clades that are less than 90% are shown, except for the C. freundii clade. Abbreviations for taxon labels, accession numbers, gene locations (plasmid or chromosome), and organism names are given in Table 1.

FIG. 2.

Bayesian consensus phylogeny of the C. freundii ampC alleles. Probabilities of clades that are less than 100% are shown. Bayesian estimates for the number of nucleotide changes that have occurred along each of the branches are also shown. Abbreviations for taxon labels, accession numbers, gene locations (plasmid or chromosome), and organism names are given in Table 1.