d-aspartate, an amino-acid important for human health, supports anaerobic respiration in several Campylobacter species.

Despite being classified as microaerophilic microorganisms, most Campylobacter species can grow anaerobically, using formate or molecular hydrogen (H) as electron donors, and various nitrogenous and sulfurous compounds as electron acceptors. Herein, we showed that both l-asparagine (l-Asn) and l-aspartic acid (l-Asp) bolster H-driven anaerobic growth in several Campylobacter species, whereas the d-enantiomer form of both asparagine (d-Asn) and aspartic acid (d-Asp) only increased anaerobic growth in Campylobacter concisus strain 13826 and Campylobacter ureolyticus strain NCTC10941. A gene annotated as racD encoding for a putative d/l-Asp racemase was identified in the genome of both strains.

The BisA protein plays a dual role: oxide-dependent anaerobic respiration and periplasmic methionine sulfoxide repair.

is an excellent model organism to study respiration diversity, including anaerobic respiration of physiologically relevant N-/S-oxides compounds, such as biotin sulfoxide, dimethyl sulfoxide, methionine sulfoxide (MetO), nicotinamide N-oxide, and trimethylamine N-oxide. All strains harbor at least two, often three, and up to five genes encoding for putative periplasmic Mo/W-bisPGD-containing N-/S-oxide reductases. The respective role (substrate specificity) of each enzyme was studied using a mutagenesis approach.

Restoring and Enhancing the Potency of Existing Antibiotics against Drug-Resistant Gram-Negative Bacteria through the Development of Potent Small-Molecule Adjuvants.

The rapid and persistent emergence of drug-resistant bacteria poses a looming public health crisis. The possible task of developing new sets of antibiotics to replenish the existing ones is daunting to say the least. Searching for adjuvants that restore or even enhance the potency of existing antibiotics against drug-resistant strains of bacteria represents a practical and cost-effective approach.

Copper toxicity towards Campylobacter jejuni is enhanced by the nickel chelator dimethylglyoxime.

The nickel (Ni)-chelator dimethylglyoxime (DMG) was found to be bacteriostatic towards Campylobacter jejuni. Supplementation of nickel to DMG-containing media restored bacterial growth, whereas supplementation of cobalt or zinc had no effect on the growth inhibition. Unexpectedly, the combination of millimolar levels of DMG with micromolar levels of copper (Cu) was bactericidal, an effect not seen in select Gram-negative pathogenic bacteria.

The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation.

One of the hallmarks of the most common neurodegenerative disease, Alzheimer's disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have a synergistic effect on the aggregation of Aβ-peptides. In the present study, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal content of a commercial recombinant human Aβ peptide.

Highly Efficient Antimicrobial Activity of CuFeO Nanoparticles against Important Human Pathogens.

The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria in a short period of time, be less or not toxic to normal cells, and the fabrication or synthesis process should be cheap and easy. We report a one-step microwave-assisted hydrothermal synthesis of mixed composite CuFeO (FeO/CuO/CuO/CuFeO) nanoparticles (NPs) as an excellent antimicrobial material.

Influence of Protein Glycosylation on Physiology.

is commonly associated with venereal disease and abortions in cattle and sheep, and can also cause intestinal or systemic infections in humans that are immunocompromised, elderly, or exposed to infected livestock. It is also believed that infection can result from the consumption or handling of contaminated food products, but is rarely detected in food since isolation methods are not suited for its detection and the physiology of the organism makes culturing difficult. In the related species, , the ability to colonize the host has been linked to N-linked protein glycosylation with quantitative proteomics demonstrating that glycosylation is interconnected with cell physiology.

Molecular Hydrogen Metabolism: a Widespread Trait of Pathogenic Bacteria and Protists.

Pathogenic microorganisms use various mechanisms to conserve energy in host tissues and environmental reservoirs. One widespread but often overlooked means of energy conservation is through the consumption or production of molecular hydrogen (H). Here, we comprehensively review the distribution, biochemistry, and physiology of H metabolism in pathogens.

Author Correction: Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens.

The nickel (Ni)-specific chelator dimethylglyoxime (DMG) has been used for many years to detect, quantitate or decrease Ni levels in various environments. Addition of DMG at millimolar levels has a bacteriostatic effect on some enteric pathogens, including multidrug resistant (MDR) strains of Salmonella Typhimurium and Klebsiella pneumoniae. DMG inhibited activity of two Ni-containing enzymes, Salmonella hydrogenase and Klebsiella urease.

Site-directed mutagenesis of Campylobacter concisus respiratory genes provides insight into the pathogen's growth requirements.

Campylobacter concisus is an emerging human pathogen found throughout the entire human oral-gastrointestinal tract. The ability of C. concisus to colonize diverse niches of the human body indicates the pathogen is metabolically versatile.

Noncatalytic Antioxidant Role for Helicobacter pylori Urease.

The well-studied catalytic role of urease, the Ni-dependent conversion of urea into carbon dioxide and ammonia, has been shown to protect against the low pH environment of the stomach lumen. We hypothesized that the abundantly expressed urease protein can play another noncatalytic role in combating oxidative stress via Met residue-mediated quenching of harmful oxidants. Three catalytically inactive urease mutant strains were constructed by single substitutions of Ni binding residues.

Iron-sulfur protein maturation in Helicobacter pylori: identifying a Nfu-type cluster carrier protein and its iron-sulfur protein targets.

Helicobacter pylori is anomalous among non nitrogen-fixing bacteria in containing an incomplete NIF system for Fe-S cluster assembly comprising two essential proteins, NifS (cysteine desulfurase) and NifU (scaffold protein). Although nifU deletion strains cannot be obtained via the conventional gene replacement, a NifU-depleted strain was constructed and shown to be more sensitive to oxidative stress compared to wild-type (WT) strains. The hp1492 gene, encoding a putative Nfu-type Fe-S cluster carrier protein, was disrupted in three different H.

Click, Release, and Fluoresce: A Chemical Strategy for a Cascade Prodrug System for Codelivery of Carbon Monoxide, a Drug Payload, and a Fluorescent Reporter.

A chemical strategy was developed wherein a single trigger sets in motion a three-reaction cascade leading to the release of more than one drug-component in sequence with the generation of a fluorescent side product for easy monitoring. As a proof of concept, codelivery of CO with the antibiotic metronidazole was demonstrated.

Structure-function analyses of metal-binding sites of HypA reveal residues important for hydrogenase maturation in Helicobacter pylori.

The nickel-containing enzymes of Helicobacter pylori, urease and hydrogenase, are essential for efficient colonization in the human stomach. The insertion of nickel into urease and hydrogenase is mediated by the accessory protein HypA. HypA contains an N-terminal nickel-binding site and a dynamic structural zinc-binding site.

Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress.

Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (HO). The gastric pathogen undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium.

Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation.

Unlabelled: A known virulence factor of Helicobacter pylori that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128.

Carbon Fixation Driven by Molecular Hydrogen Results in Chemolithoautotrophically Enhanced Growth of Helicobacter pylori.

Unlabelled: A molecular hydrogen (H2)-stimulated, chemolithoautotrophic growth mode for the gastric pathogen Helicobacter pylori is reported. In a culture medium containing peptides and amino acids, H2-supplied cells consistently achieved 40 to 60% greater growth yield in 16 h and accumulated 3-fold more carbon from [(14)C]bicarbonate (on a per cell basis) in a 10-h period than cells without H2 Global proteomic comparisons of cells supplied with different atmospheric conditions revealed that addition of H2 led to increased amounts of hydrogenase and the biotin carboxylase subunit of acetyl coenzyme A (acetyl-CoA) carboxylase (ACC), as well as other proteins involved in various cellular functions, including amino acid metabolism, heme synthesis, or protein degradation. In agreement with this result, H2-supplied cells contained 3-fold more ACC activity than cells without H2 Other possible carbon dioxide (CO2) fixation enzymes were not up-expressed under the H2-containing atmosphere.

Host hydrogen rather than that produced by the pathogen is important for Salmonella enterica serovar Typhimurium virulence.

Salmonella enterica serovar Typhimurium utilizes molecular hydrogen as a substrate in various respiratory pathways, via H2-uptake enzymes termed Hya, Hyb, and Hyd. A different hydrogenase, the hydrogen-evolving Hyc enzyme, removes excess reductant during fermentative growth. Virulence phenotypes conferred by mutations in hyc genes, either alone or in combination with mutations in the H2-uptake enzyme genes, are addressed.

Twin-arginine translocation system in Helicobacter pylori: TatC, but not TatB, is essential for viability.

Unlabelled: The twin-arginine translocation (Tat) system, needed to transport folded proteins across biological membranes, has not been characterized in the gastric pathogen Helicobacter pylori. Analysis of all H. pylori genome sequences available thus far reveals the presence of single copies of tatA, tatB, and tatC needed for the synthesis of a fully functional Tat system.

A link between gut community metabolism and pathogenesis: molecular hydrogen-stimulated glucarate catabolism aids Salmonella virulence.

Glucarate, an oxidized product of glucose, is a major serum organic acid in humans. Still, its role as a carbon source for a pathogen colonizing hosts has not been studied. We detected high-level expression of a potential glucarate permease encoding gene gudT when Salmonella enterica serovar Typhimurium are exposed to hydrogen gas (H(2)), a gaseous by-product of gut commensal metabolism.

Alkyl hydroperoxide reductase repair by Helicobacter pylori methionine sulfoxide reductase.

Protein exposure to oxidants such as HOCl leads to formation of methionine sulfoxide (MetSO) residues, which can be repaired by methionine sulfoxide reductase (Msr). A Helicobacter pylori msr strain was more sensitive to HOCl-mediated killing than the parent. Because of its abundance in H.

Random and site-specific mutagenesis of the Helicobacter pylori ferric uptake regulator provides insight into Fur structure-function relationships.

The ferric uptake regulator (Fur) of Helicobacter pylori is a global regulator that is important for colonization and survival within the gastric mucosa. H. pylori Fur is unique in its ability to activate and repress gene expression in both the iron-bound (Fe-Fur) and apo forms (apo-Fur).

Helicobacter pylori stores nickel to aid its host colonization.

The transition metal nickel (Ni) is critical for the pathogenicity of Helicobacter pylori. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for in vivo colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular H.