Cu Homeostasis in Bacteria: The Ins and Outs

Andrei, Andreea; Öztürk, Yavuz; Khalfaoui-Hassani, Bahia; Rauch, Juna; Marckmann, Dorian; Trasnea, Petru‐Iulian; Daldal, Fevzi; Koch, Hans‐Georg

doi:10.3390/membranes10090242

Cited by 90 publications

(108 citation statements)

References 360 publications

(597 reference statements)

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“…Therefore, P. aeruginosa develops and maintains a complex copper homeostasis to preserve the thin line between essential copper concentrations and excess of copper ( Figure 1 ). It is a topic of current research to verify and understand the detailed mechanisms responsible for copper uptake in bacteria [ 72 ]. To date, there is a common understanding that porins, such as oprC, are responsible for the majority of copper detected in bacteria [ 72 , 73 , 74 ].…”

Section: Copper Importmentioning

confidence: 99%

“…It is a topic of current research to verify and understand the detailed mechanisms responsible for copper uptake in bacteria [ 72 ]. To date, there is a common understanding that porins, such as oprC, are responsible for the majority of copper detected in bacteria [ 72 , 73 , 74 ]. Very recent advances suggest that the TonB-dependent transporter oprC can bind to Cu(I) and mediate the import and oxidation to Cu(II) (6).…”

Section: Copper Importmentioning

confidence: 99%

“…PcoA (PA2065) and pcoB (PA2064) are both outer transmembrane-spanning proteins responsible for reducing copper concentrations in the periplasm by excretion and oxidation, respectively ( Figure 1 ) [ 72 , 128 ]. It is thought that these two membrane proteins are in close interaction and might orchestrate the export and redox reaction of copper [ 128 , 129 , 130 ].…”

Section: Copper Defense Mechanisms In P Aeruginosamentioning

confidence: 99%

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Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Hofmann

Hirsch

Ruthstein

2021

IJMS

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Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.

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Section: Copper Importmentioning

confidence: 99%

Section: Copper Importmentioning

confidence: 99%

Section: Copper Defense Mechanisms In P Aeruginosamentioning

confidence: 99%

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Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Hofmann

Hirsch

Ruthstein

2021

IJMS

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“…This bactericidal activity is concentration-dependent. Indeed, at low concentrations, copper plays an important role in the life of bacteria as it is involved in a number of their metalloenzymes called cuproenzymes [ 11 , 12 ]. However, at high concentrations, copper ions overcome the bacterial handling/detoxification systems and are able to generate a wide array of detrimental perturbations for the bacterial cell such as mismetalation of metalloenzymes induced by the ionic imbalance or excessive production of reactive oxygen species (ROS) initiated through a Fenton-like reaction.…”

Section: Introductionmentioning

confidence: 99%

Brass Alloys: Copper-Bottomed Solutions against Hospital-Acquired Infections?

Dauvergne

Mullié

2021

Antibiotics

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Copper has been used for its antimicrobial properties since Antiquity. Nowadays, touch surfaces made of copper-based alloys such as brasses are used in healthcare settings in an attempt to reduce the bioburden and limit environmental transmission of nosocomial pathogens. After a brief history of brass uses, the various mechanisms that are thought to be at the basis of brass antimicrobial action will be described. Evidence shows that direct contact with the surface as well as cupric and cuprous ions arising from brass surfaces are instrumental in the antimicrobial effectiveness. These copper ions can lead to oxidative stress, membrane alterations, protein malfunctions, and/or DNA damages. Laboratory studies back up a broad spectrum of activity of brass surfaces on bacteria with the possible exception of bacteria in their sporulated form. Various parameters influencing the antimicrobial activity such as relative humidity, temperature, wet/dry inoculation or wear have been identified, making it mandatory to standardize antibacterial testing. Field trials using brass and copper surfaces consistently report reductions in the bacterial bioburden but, evidence is still sparse as to a significant impact on hospital acquired infections. Further work is also needed to assess the long-term effects of chemical/physical wear on their antimicrobial effectiveness.

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“…As an example, the innate phagocyte (alveolar macrophages and neutrophils) defense utilizes – in addition to other mechanisms – copper as a microbial toxin ( Ding et al, 2014 ; García-Santamarina and Thiele, 2015 ). Consequently, all organisms have developed mechanisms to elude or alleviate Cu toxicity and intoxification ( Garcia et al, 2014 ; Smith et al, 2017 ; Andrei et al, 2020 ; Linder, 2020 ). Some fungi – especially unicellular yeasts – produce copper-binding metallothioneins to modulate the concentration of the free cation ( Mackie et al, 2016 ), whereas multicellular filamentous fungi (such as A. fumigatus and Fusarium oxysporum ) make use of Cu 2+ -exporting ATPases (EC 7.2.2.9) to maintain intracellular copper homeostasis ( Wiemann et al, 2017 ; Lorenzo-Gutiérrez et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Carbon-Source Dependent Interplay of Copper and Manganese Ions Modulates the Morphology and Itaconic Acid Production in Aspergillus terreus

et al. 2021

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The effects of the interplay of copper(II) and manganese(II) ions on growth, morphology and itaconic acid formation was investigated in a high-producing strain of Aspergillus terreus (NRRL1960), using carbon sources metabolized either mainly via glycolysis (D-glucose, D-fructose) or primarily via the pentose phosphate shunt (D-xylose, L-arabinose). Limiting Mn2+ concentration in the culture broth is indispensable to obtain high itaconic acid yields, while in the presence of higher Mn2+ concentrations yield decreases and biomass formation is favored. However, this low yield in the presence of high Mn2+ ion concentrations can be mitigated by increasing the Cu2+ concentration in the medium when D-glucose or D-fructose is the growth substrate, whereas this effect was at best modest during growth on D-xylose or L-arabinose. A. terreus displays a high tolerance to Cu2+ which decreased when Mn2+ availability became increasingly limiting. Under such conditions biomass formation on D-glucose or D-fructose could be sustained at concentrations up to 250 mg L–1 Cu2+, while on D-xylose- or L-arabinose biomass formation was completely inhibited at 100 mg L–1. High (>75%) specific molar itaconic acid yields always coincided with an “overflow-associated” morphology, characterized by small compact pellets (<250 μm diameter) and short chains of “yeast-like” cells that exhibit increased diameters relative to the elongated cells in growing filamentous hyphae. At low concentrations (≤1 mg L–1) of Cu2+ ions, manganese deficiency did not prevent filamentous growth. Mycelial- and cellular morphology progressively transformed into the typical overflow-associated one when external Cu2+ concentrations increased, irrespective of the available Mn2+. Our results indicate that copper ions are relevant for overflow metabolism and should be considered when optimizing itaconic acid fermentation in A. terreus.

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Cu Homeostasis in Bacteria: The Ins and Outs

Cited by 90 publications

References 360 publications

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Brass Alloys: Copper-Bottomed Solutions against Hospital-Acquired Infections?

Carbon-Source Dependent Interplay of Copper and Manganese Ions Modulates the Morphology and Itaconic Acid Production in Aspergillus terreus

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