Inhibiting the copper efflux system in microbes as a novel approach for developing antibiotics

Meir, Aviv; Lepechkin-Zilbermintz, Veronica; Kahremany, Shirin; Schwerdtfeger, Fabian; Gevorkyan‐Airapetov, Lada; Munder, Anna; Viskind, Olga; Gruzman, Arie; Ruthstein, Sharon

doi:10.1101/763185

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…[ 32 ] Remarkably, the complexation of copper with the cyanine derivatives demonstrates, similar to other reported copper complexes, the important role of complexation in the development of new synergistic antimicrobial strategies, by promoting the protection of copper ions for an effective incorporation inside bacteria and increases the amount of reactive oxygen species. [ 32,33 ] Derivatives 2‐Cu and 3‐Cu showed antibacterial activity against all tested bacterial strains, suggesting a non‐selective inhibitory behavior for bacterial growth. Besides P. aeruginosa , the presence of copper decreases the MIC 50 of derivative 3 in E. faecalis , L. monocytogenes , and B. cereus .…”

Section: Resultsmentioning

confidence: 99%

Functional Cyanine‐Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health‐Care Bacterial Infections

Marcelo

Galhano

Duarte

et al. 2022

Macromolecular Bioscience

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The rising of multidrug-resistant bacteria and their associated proliferation as harmful microorganisms boosts the creation of new antibacterial surfaces and biomaterials with applications ranging from health to food packing. Herein, low-cost antibacterial PVA:PVP copolymers containing cyanine derivatives (1, 2, and 3) and their respective Cu 2+ complexes are successfully obtained and tested against Gram-negative and Gram-positive bacteria. The possible application in food packing is addressed by covering the surface of typical paper mockups with the doped polymers. All dye-doped polymers present a broad-spectrum antibacterial effect against Gram-positive bacteria, especially for Bacillus cereus (B. cereus), Staphylococcus aureus (S. aureus), and methicillin-resistant S. aureus (MRSA) strains, with PVA:PVP@3 and PVA:PVP@3-Cu being the most effective. Moreover, polymers containing cyanine derivatives present interesting inhibition effects against Pseudomonas aeruginosa (P. aeruginosa), where the production of its characteristic blue/green virulent pigment is not observed.

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Section: Resultsmentioning

confidence: 99%

Functional Cyanine‐Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health‐Care Bacterial Infections

Marcelo

Galhano

Duarte

et al. 2022

Macromolecular Bioscience

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“…Cu homeostasis is therefore highly relevant, since it could also provide valuable targets for novel antibacterial drugs, as recently reported for the Cu export system [6]. Most known cuproproteins are located in the bacterial envelope, therefore an efficient Cu homeostasis system is required in this compartment to protect cells form Cu toxicity and to provide Cu cofactor to fulfil protein function.…”

Section: Introductionmentioning

confidence: 92%

A periplasmic cupredoxin with a green CuT1.5 center is involved in bacterial copper tolerance

et al. 2021

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Importance of copper resistance pathways in pathogenic bacteria is now well recognized since macrophages use copper to fight bacterial infections. Additionally, considering the increase of antibiotic resistance, growing attention is given to the antimicrobial properties of copper. It is of primary importance to understand how bacteria deal with copper. The Cu resistant cuproprotein CopI is present in many Human bacterial pathogens and environmental bacteria and crucial under microaerobiosis (conditions for most pathogens to thrive within their host). Hence, understanding its mechanism of function is essential. CopI proteins share conserved histidine, cysteine and methionine residues that could be ligands for different copper binding sites among which acupredoxin center that could be involved in the protein function. Here, we demonstrated that, Vibrio cholerae and Pseudomonas aeruginosa CopI restore Cu resistance phenotype in Rubrivivax (R.) gelatinosus ΔcopI mutant. We identified that Cys125 (ligand in the cupredoxin center) and conserved histidines and methionines are essential for R. gelatinosus CopI (RgCopI) function. We also performed spectroscopic analyses of the purified RgCopI protein and showed that it is a green cupredoxin able to bind a maximum of three Cu(II) ions: (i) a green Cu site (CuT1.5), (ii) a type 2 Cu binding site (T2) located in the N-terminal region, (iii) a third site with a yet unidentified location. CopI is therefore one member of the poorly described CuT1.5 center cupredoxin family. It is unique, since it is a single domain cupredoxin with more than one Cu site involved in Cu resistance.

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“…Actually, like iron, copper is known to produce Reactive Oxygen Species (ROS) via Fenton chemistry in vitro, potentially occurring in vivo in Gram-negative bacteria and inducing copper toxicity in aerobic conditions [3]. On the other hand, copper toxicity for cells is at the origin of attractive strategies to develop novel antibacterial solutions in therapeutic approaches or in agriculture [4]. Among the different systems involved in copper tolerance in bacteria, the copper efflux oxidase (CueO) couples in vivo the oxidation of toxic Cu + to the reduction of O2 into water [1,3,5].…”

Section: Introductionmentioning

confidence: 99%

Electrochemistry of copper efflux oxidase-like multicopper oxidases involved in copper homeostasis

Mazurenko

Adachi

Ezraty

et al. 2022

Current Opinion in Electrochemistry

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Inhibiting the copper efflux system in microbes as a novel approach for developing antibiotics

Abstract: 22

Cited by 6 publications

References 56 publications

Functional Cyanine‐Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health‐Care Bacterial Infections

Functional Cyanine‐Based PVA:PVP Polymers as Antimicrobial Tools toward Food and Health‐Care Bacterial Infections

A periplasmic cupredoxin with a green CuT1.5 center is involved in bacterial copper tolerance

Electrochemistry of copper efflux oxidase-like multicopper oxidases involved in copper homeostasis

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