Origin and Evolution of the AmpC β-Lactamases ofCitrobacter freundii

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Abstract
To determine whether the widespread clinical use of β-lactams has been selective forCitrobacter freundii-derived alleles of plasmidampCgenes, we generated a Bayesian consensus phylogeny of the publishedampCsequences and compared the MICs of 16 β-lactam antibiotics forEscherichia colistrains containing cloned copies of theC. freundii ampCalleles. We found that for the majority of compounds investigated, there has been essentially no increase in β-lactam resistance conferred by those alleles. We also found thatampCalleles from the chromosomes of two β-lactam-sensitiveC. freundiistrains isolated in the 1920s, before the clinical use of antibiotics, were as effective at providing β-lactam resistance inE. colias were the plasmid-borne alleles from β-lactam-resistant clinical isolates. These results suggest that selection for increased resistance to β-lactam antibiotics has not been a significant force directing the evolution of theC. freundii ampCalleles found in β-lactam-resistant clinical isolates.