Mc. Negri et al., Concentration-dependent selection of small phenotypic differences in TEM beta-lactamase-mediated antibiotic resistance, ANTIM AG CH, 44(9), 2000, pp. 2485-2491
In this paper, the first robust experimental evidence of in vitro and in vi
vo concentration-dependent selection of low-level antibiotic-resistant gene
tic variants is described. The work is based on the study of an asymmetric
competition assay with pairs of isogenic Escherichia coli strains, differin
g only (apart from a neutral chromosomal marker) in a single amino acid rep
lacement in a plasmid-mediated TEM-1 beta-lactamase enzyme, which results i
n the new TEM-12 beta-lactamase, The mixture was challenged by different an
tibiotic concentrations, both in vitro and in the animal model, and the sel
ective process of the variant population was carefully monitored, A mathema
tical model was constructed to test the hypothesis that measured growth and
killing rates of the individual TEM variants at different antibiotic conce
ntrations could be used to predict quantitatively the strength of selection
for TEM-12 observed in competition experiments at these different concentr
ations.