Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals.
Bottom Line: This finding indicates that the very low antibiotic and heavy metal levels found in polluted environments and in treated humans and animals might be sufficiently high to maintain multiresistance plasmids.By studying the effect of combinations of several compounds, it was observed that for certain combinations of drugs each new compound added lowered the minimal selective concentration of the others.This combination effect could be a significant factor in the selection of multidrug resistance plasmids/bacterial clones in complex multidrug environments.
Affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.Show MeSH
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Mentions: To further elucidate the dependence of MSC on the fitness cost of resistance, three of the resistance cassettes, tetRA (tetracycline resistance), dhfr (trimethoprim resistance), and the mph operon (erythromycin resistance), were transferred from the pUUH239.2 plasmid to the Escherichia coli chromosome by genetic recombineering (59). The results of the competitions between these strains and isogenic susceptible strains are shown in Fig. 3. These data demonstrate that the MSC is directly dependent on the fitness cost of the resistance. Thus, when the fitness cost conferred by the rest of the plasmid is eliminated, the selection coefficient curve is shifted upwards, thereby reducing the MSC value. For tetracycline, the MSC value was 1/25 of the MICsusc (Fig. 3A); for trimethoprim, the value was less than 1/100 (Fig. 3B); and for erythromycin, the value was less than 1/60 (Fig. 3C). These values represent absolute antibiotic concentrations of 30 ng/ml (tetracycline), less than 2 ng/ml (trimethoprim), and less than 200 ng/ml (erythromycin) for the chromosomally carried resistance compared to 45 ng/ml (tetracycline), 33 ng/ml (trimethoprim), and 3,000 ng/ml (erythromycin) when the corresponding resistance was present on the plasmid. As these resistance genes on the chromosome do not confer any significant fitness costs, the MSC values approach zero, making the MSC values for trimethoprim and erythromycin uncertain in this low range.
Affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.