Abstract
ABSTRACTAntimicrobial resistance is a major health care problem, with the intensive use of heavy metals and biocides recently identified as a potential factor contributing to the aggravation of this situation. The present study investigated heavy metal susceptibility and genetic resistance determinants in Escherichia coli isolated from clinical urine samples from Sweden, Germany, and Spain. A total of 186 isolates were tested for their sodium arsenite, silver nitrate, and copper(II) sulfate MICs. In addition, 88 of these isolates were subjected to whole-genome sequencing for characterization of their genetic resistance determinants and epidemiology. For sodium arsenite, the isolates could be categorized into a resistant and a nonresistant group based on MIC values. Isolates of the resistant group exhibited the chromosomal ars operon and belonged to non-B2 phylogenetic groups; in contrast, within the B2 phylogroup, no ars operon was found, and the isolates were susceptible to sodium arsenite. Two isolates also harbored the silver/copper resistance determinant pco/sil, and they belonged to sequence types ST10 (phylogroup A) and ST295 (phylogroup C). The ST295 isolate had a silver nitrate MIC of ≥512 mg/liter and additionally produced extended-spectrum beta-lactamases. To our knowledge, this is the first study to describe the distribution of the arsenic resistance ars operon within phylogroups of E. coli strains isolated from patients with urinary tract infections. The arsenic resistance ars operon was present only in all non-B2 clades, which have previously been associated with the environment and commensalism in both humans and animals, while B2 clades lacked the ars operon.
Highlights
Antimicrobial resistance is a major health care problem, with the intensive use of heavy metals and biocides recently identified as a potential factor contributing to the aggravation of this situation
In the present study, heavy metal resistance in E. coli isolates from urine samples was strongly associated with phylogenetic clades which have previously been associated with the environment and commensalism and reflect the selective pressure to which bacteria are exposed
The isolates in the more resistant group possessed the chromosomal ars operon and belonged to non-B2 phylogenetic groups of E. coli, which have previously been associated with the environment and commensalism, whereas the arsenic-susceptible aac.asm.org 5
Summary
Antimicrobial resistance is a major health care problem, with the intensive use of heavy metals and biocides recently identified as a potential factor contributing to the aggravation of this situation. The ST295 isolate had a silver nitrate MIC of Ն512 mg/liter and produced extended-spectrum beta-lactamases To our knowledge, this is the first study to describe the distribution of the arsenic resistance ars operon within phylogroups of E. coli strains isolated from patients with urinary tract infections. Heavy metal exposure levels are sublethal for bacteria, making them possible resistance-driving mechanisms [19] Nonspecific mechanisms, such as reduced permeation ability or uptake and enhanced efflux [20, 21] or shared mobile genetic elements [15, 22,23,24], are able to mediate resistance to both heavy metals and antimicrobials. It is hard to predict what impact increased exposure to heavy metals has on the development and spread of new potent clinical isolates, especially because resistance data for heavy metals are only infrequently obtained
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