Copper-responsive gene regulation in bacteria

Rademacher, Corinna; Masepohl, Bernd

doi:10.1099/mic.0.058487-0

Cited by 161 publications

(160 citation statements)

References 85 publications

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“…High copper levels are toxic, and bacteria have evolved copper resistance and translocation systems that function to equilibrate the intracellular copper levels. In E. coli, the CopACueO and CusCFBA systems are involved in protecting the bacterium during exposure to moderate and high copper concentrations under aerobic and anaerobic conditions, respectively (43). Our transcriptomic analysis showed that the Cop system is differentially regulated in the ⌬tatC mutant.…”

Section: Figmentioning

confidence: 83%

Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis

et al. 2016

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The twin-arginine translocation (Tat) system mediates the secretion of folded proteins that are identified via an N-terminal signal peptide in bacteria, plants, and archaea. Tat systems are associated with virulence in many bacterial pathogens, and our previous studies revealed that Tat-deficient Yersinia pseudotuberculosis was severely attenuated for virulence. Aiming to identify Tat-dependent pathways and phenotypes of relevance for in vivo infection, we analyzed the global transcriptome of parental and ⌬tatC mutant strains of Y. pseudotuberculosis during exponential and stationary growth at 26°C and 37°C. The most significant changes in the transcriptome of the ⌬tatC mutant were seen at 26°C during stationary-phase growth, and these included the altered expression of genes related to virulence, stress responses, and metabolism. Subsequent phenotypic analysis based on these transcriptome changes revealed several novel Tat-dependent phenotypes, including decreased YadA expression, impaired growth under iron-limited and high-copper conditions, as well as acidic pH and SDS. Several functionally related Tat substrates were also verified to contribute to these phenotypes. Interestingly, the phenotypic defects observed in the Tat-deficient strain were generally more pronounced than those in mutants lacking the Tat substrate predicted to contribute to that specific function. Altogether, this provides new insight into the impact of Tat deficiency on in vivo fitness and survival/replication of Y. pseudotuberculosis during infection. IMPORTANCEIn addition to its established role in mediating the secretion of housekeeping enzymes, the Tat system has been recognized as being involved in infection. In some clinically relevant bacteria, such as Pseudomonas spp., several key virulence determinants can readily be identified among the Tat substrates. In enteropathogens, such as Yersinia spp., there are no obvious virulence determinants among the Tat substrates. Tat mutants show no growth defect in vitro but are highly attenuated in in vivo. This makes Tat an attractive target for the development of novel antimicrobials. Therefore, it is important to establish the causes of the attenuation. Here, we show that the attenuation is likely due to synergistic effects of different Tat-dependent phenotypes that each contributes to lowered in vivo fitness. Bacteria have evolved several specialized secretion systems for protein export as part of their successful strategies to colonize niches where they encounter various environmental conditions. Gram-negative bacteria possess different mechanisms to transport/export proteins, including virulence-related factors from the cytoplasm across the inner membrane and/or the outer membrane, either in a single step or acting together with other secretion systems (1). Two pathways, the secretory (Sec) and the twin-arginine translocation (Tat) pathways, are involved in the translocation of proteins from the cytoplasm to the periplasm. In Gramnegative bacteria, they can cooperate with other s...

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Section: Figmentioning

confidence: 83%

Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis

et al. 2016

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“…It is known that bacteria have strict control over the transport of copper (Input-Output), ensuring the homeostasis required for protein synthesis and prevention of toxic effects, by a highly controlled system of transcriptional regulators, soluble chaperone, membrane transporters, and cooper proteins distributed in various bacterial compartments (Rademacher et al, 2012;Elguindi et al, 2011). Most bacteria synthesize P-type ATPase export of copper as main determinants of defense when copper concentrations are higher than average.…”

Section: Discussionmentioning

confidence: 99%

Copper Nanoparticles as Potential Antimicrobial Agent in Disinfecting Root Canals: A Systematic Review

Sánchez‐Sanhueza

Fuentes‐Rodríguez

Bello-Toledo

2016

Int. J. Odontostomat.

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ABSTRACT:Copper was registered as the first solid antimicrobial material. Its availability makes it an important option as an antibacterial agent. At nanoparticle size it does not exceed 100 nm, allowing close interaction with microbial membranes, enhancing its effect even more. Copper generates toxic hydroxyl radicals that damage cell membranes of Gram-negative and Gram-positive bacteria, among the latter, Enterococcus faecalis, which are present in infected radicular canals. Synthesis of metal nanoparticles with antimicrobial properties has become a viable alternative and has promising applications in the fight against pathogenic microorganisms. Furthermore, the use of some polymers to stabilize nanoparticles increases their release time and may as well decrease the risk of bacterial recolonization and biofilm formation within the ducts, enhancing the antimicrobial properties of these compounds.The aim of this article is to conduct a systematic review of the literature on antimicrobial copper nanoparticles, their current applications and their potential use in the area of oral health, specifically in the field of endodontics.

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“…The RicR regulon includes the genes encoding a mycobacterium-specific cytoplasmic copper metallothioneine (MymT) and a periplasmic multicopper oxidase (MmcO) (10,20,21). Although copper resistance pathways are of great interest (reviewed in reference [22][23][24], little has been done to investigate how copper enters bacterial cells to be utilized metabolically or to exert its bactericidal properties.…”

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confidence: 99%

Porins Increase Copper Susceptibility of Mycobacterium tuberculosis

et al. 2013

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cCopper resistance mechanisms are crucial for many pathogenic bacteria, including Mycobacterium tuberculosis, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in Mycobacterium smegmatis leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene mspA reduced growth of M. tuberculosis in the presence of 2.5 M copper by 40% and completely suppressed growth at 15 M copper, while wild-type M. tuberculosis reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M. tuberculosis for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of M. tuberculosis to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in M. smegmatis and M. tuberculosis.

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Copper-responsive gene regulation in bacteria

Cited by 161 publications

References 85 publications

Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis

Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway in Yersinia pseudotuberculosis

Copper Nanoparticles as Potential Antimicrobial Agent in Disinfecting Root Canals: A Systematic Review

Porins Increase Copper Susceptibility of Mycobacterium tuberculosis

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