Copper Kills Escherichia coli Persister Cells

Abstract

Due to their reduced metabolism, persister cells can survive most antimicrobial treatments, which usually rely on corrupting active biochemical pathways. Therefore, molecules that kill bacterial persisters should function in a metabolism-independent manner. Some anti-persister compounds have been found previously, such as the DNA-crosslinkers mitomycin C and cisplatin, but more effective and lower cost alternatives are needed. Copper alloys have been used since ancient times due to their antimicrobial properties, and they are still used in agriculture to control plant bacterial diseases. By stopping transcription with rifampicin and by treating with ampicillin to remove non-persister cells, we created a population that consists solely of Escherichia coli persister cells. Using this population of persister cells, we demonstrate that cupric compounds kill E. coli persister cells. Hence, copper ions may be used in controlling the spread of important bacterial strains that withstand treatment with conventional antimicrobials by forming persister cells.

Persister Cells Form in the Plant Pathogen Xanthomonas citri subsp. citri under Different Stress Conditions

“…In order to study persistence in bacteria, it is necessary to increase its proportion in a given population. As a proof of concept, we applied the same method previously utilized in E. coli [18,43,44]. The basic principle behind this technique is that if persister cells are formed by given stress, they can withstand a subsequent treatment with another antibiotic and are killed to a lesser extent than control cells (those not receiving the persister-inducing stress).…”

Evaluation of Kdo-8-N3 incorporation into lipopolysaccharides of various Escherichia coli strains

“…The copper-catalyzed click reaction resulted in a very faint band on the gel image (Fig. 6-I: A, lane 5), which we hypothesize is due to loss of LPS as a result of cell lysis or membrane damage during the incubation with copper, 27–29 as the amounts of LPS after copper-catalyzed click reactions were generally lower. To reduce potential toxicity, the copper-catalyzed click reaction may be improved by further optimizing the copper to ligand ratio, or by the use of alternative ligands such as BTTP and BTTAA.…”

Experimental Evolution of Copper Resistance in Escherichia coli Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide

“…Even less attention has been paid to how evolved copper resistance may produce correlated resistances to other antimicrobials. Previous studies demonstrated that copper—in ionic and nanoparticles forms—is antibacterial, with MICs ranging from 32 µL/mL to 960 µg/mL [ 26 , 27 , 28 ]. Here, we showed that Cu resistance evolved rapidly in E. coli after 37 days of selection at a sub-inhibitory concentration of 75 mg/L CuSO 4 , via de novo mutations and gene expression changes.…”