Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria

Crane, John K.; Cheema, Muhammad B; Olyer, Michael A; Sutton, Mark D.

doi:10.3389/fcimb.2018.00410

Cited by 35 publications

(48 citation statements)

References 33 publications

(48 reference statements)

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“…Reduced plasmid transfer in response to metal stress could be a consequence of changes in metabolic status, decrease in plasmid replication, activation of the SOSresponse, or a combination of different mechanisms. [56][57][58] This study also showed that both the IncK and IncI1 plasmids remained stable in their host throughout several generations, independent of presence of Zn or Cu.…”

Section: Discussionsupporting

confidence: 62%

Zinc and Copper Reduce Conjugative Transfer of Resistance Plasmids from Extended-Spectrum Beta-Lactamase-Producing Escherichia coli

Buberg

Witsø

L’Abée-Lund

et al. 2020

Microbial Drug Resistance

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The present work addresses the effect of excess levels of ZnCl 2 and CuSO 4 in the growth medium on the conjugative transfer of plasmids carrying the antibiotic resistance gene bla CMY-2 from extended-spectrum betalactamase (ESBL)-producing Escherichia coli. Norwegian poultry are not treated prophylactically with antibiotics, but still, ESBL-producing E. coli are found in the chicken populations. Chickens receive higher amounts of Zn and Cu than their biological need, and several metals have been shown to act as drivers of antimicrobial resistance. In the present study, ESBL-producing E. coli strains collected from retail chicken meat were mated in broth containing various concentrations of ZnCl 2 and CuSO 4 . Manual counting of transconjugants showed that ZnCl 2 and CuSO 4 reduced the conjugation frequency between E. coli strains in a concentration-dependent manner. Quantitative real-time PCR analyses showed that the presence of ZnCl 2 and CuSO 4 in the growth media reduced expression of the conjugation genes traB and nikB. By propagating monocultures over several generations, it was found that the bla CMY-2 plasmids remained stable in the recipient strains. Together the results show that exposure of ESBL-producing E. coli to Zn and Cu reduce horizontal transfer of the bla CMY-2 resistance plasmid by reducing expression of genes involved in conjugation in the plasmid donor strain.

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Section: Discussionsupporting

confidence: 62%

Zinc and Copper Reduce Conjugative Transfer of Resistance Plasmids from Extended-Spectrum Beta-Lactamase-Producing Escherichia coli

Buberg

Witsø

L’Abée-Lund

et al. 2020

Microbial Drug Resistance

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“…The SOS response consists of an orchestrated pathway, performed by a multiprotein complex that is coordinately activated by the bacteria, in response to various conditions that induce DNA damage or blockage, in the cell replication (as antibiotic treatment) [13,14,15]. This pathway is activated by the accumulation of single-stranded DNAs (ss-DNA) that are bound by RecA, and this complex induces the auto-cleavage of the LexA protein [16,17]. After this, the expression of SOS-related genes is activated, resulting in the inhibition of the cell division process, in order to repair the DNA [13,18].…”

Section: Introductionmentioning

confidence: 99%

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

et al. 2019

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The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies.

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“…The SOS response is involved in bacterial adaptive responses and horizontal gene transfer, potentially leading to the onset of antibiotic resistance in a broad range of bacterial species. Recent studies have shown that zinc is efficient at inhibiting both resistance mutation induced by quinolones in E. coli and Klebsiella pneumoniae (14) and SOS-induced development of chloramphenicol resistance in Enterobacter cloacae (12). Additionally, the same authors also showed that zinc was able to inhibit the transfer of an extended spectrum beta-lactamase (ESBL) gene from Enterobacter cloacae to E. coli (12).…”

Section: Discussionmentioning

confidence: 98%

“…Recent studies have shown that zinc is efficient at inhibiting both resistance mutation induced by quinolones in E. coli and Klebsiella pneumoniae (14) and SOS-induced development of chloramphenicol resistance in Enterobacter cloacae (12). Additionally, the same authors also showed that zinc was able to inhibit the transfer of an extended spectrum beta-lactamase (ESBL) gene from Enterobacter cloacae to E. coli (12). At much higher concentrations than the one used in our study, zinc has a direct antibacterial and antibiofilm activity (24).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to tolerance, the SOS response has been shown to be involved in horizontal gene transfer, emergence of antibiotic resistance, and toxin production (10). Several candidate inhibitors of the SOS response have been reported, including zinc, for which the molecular details of activity have been well described (11)(12)(13)(14)(15). Zinc inhibits the SOS response by interfering with the RecA ATP-binding site, which is essential for RecA activation (14).…”

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confidence: 99%

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Zinc Acetate Potentiates the Action of Tosufloxacin against Escherichia coli Biofilm Persisters

Usui

Yokoo

Tsutsumi

et al. 2019

Antimicrob Agents Chemother

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Formation of bacterial biofilms is a major health threat due to their high levels of tolerance to multiple antibiotics and the presence of persisters responsible for infection relapses. We previously showed that a combination of starvation and induction of SOS response in biofilm led to increased levels of persisters and biofilm tolerance to fluoroquinolones. In this study, we hypothesized that inhibition of the SOS response may be an effective strategy to target biofilms and fluoroquinolone persister cells. We tested the survival of Escherichia coli biofilms to different classes of antibiotics in starved and nonstarved conditions and in the presence of zinc acetate, a SOS response inhibitor. We showed that zinc acetate potentiates, albeit moderately, the activity of fluoroquinolones against E. coli persisters in starved biofilms. The efficacy of zinc acetate to increase fluoroquinolone activity, particularly that of tosufloxacin, suggests that such a combination may be a potential strategy for treating biofilm-related bacterial infections.

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Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria

Cited by 35 publications

References 33 publications

Zinc and Copper Reduce Conjugative Transfer of Resistance Plasmids from Extended-Spectrum Beta-Lactamase-Producing Escherichia coli

Zinc and Copper Reduce Conjugative Transfer of Resistance Plasmids from Extended-Spectrum Beta-Lactamase-Producing Escherichia coli

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

Zinc Acetate Potentiates the Action of Tosufloxacin against Escherichia coli Biofilm Persisters

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