scholarly journals Faculty Opinions recommendation of Molecular hydrogen metabolism: a widespread trait of pathogenic bacteria and protists.

2021 ◽  
Author(s):  
Michael Maroney
Keyword(s):  
Molecular Hydrogen ◽  
Pathogenic Bacteria ◽  
Hydrogen Metabolism

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

2020 ◽  
Vol 84 (1) ◽  
Author(s):  
Stéphane L. Benoit ◽  
Robert J. Maier ◽  
R. Gary Sawers ◽  
Chris Greening
Keyword(s):  
Molecular Hydrogen ◽  
Trichomonas Vaginalis ◽  
Pathogenic Bacteria ◽  
Anaerobic Bacteria ◽  
Anaerobic Respiration ◽  
Hydrogen Metabolism ◽  
Human Pathogens ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Holistic Understanding

SUMMARY 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 (H2). Here, we comprehensively review the distribution, biochemistry, and physiology of H2 metabolism in pathogens. Over 200 pathogens and pathobionts carry genes for hydrogenases, the enzymes responsible for H2 oxidation and/or production. Furthermore, at least 46 of these species have been experimentally shown to consume or produce H2. Several major human pathogens use the large amounts of H2 produced by colonic microbiota as an energy source for aerobic or anaerobic respiration. This process has been shown to be critical for growth and virulence of the gastrointestinal bacteria Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Campylobacter concisus, and Helicobacter pylori (including carcinogenic strains). H2 oxidation is generally a facultative trait controlled by central regulators in response to energy and oxidant availability. Other bacterial and protist pathogens produce H2 as a diffusible end product of fermentation processes. These include facultative anaerobes such as Escherichia coli, S. Typhimurium, and Giardia intestinalis, which persist by fermentation when limited for respiratory electron acceptors, as well as obligate anaerobes, such as Clostridium perfringens, Clostridioides difficile, and Trichomonas vaginalis, that produce large amounts of H2 during growth. Overall, there is a rich literature on hydrogenases in growth, survival, and virulence in some pathogens. However, we lack a detailed understanding of H2 metabolism in most pathogens, especially obligately anaerobic bacteria, as well as a holistic understanding of gastrointestinal H2 transactions overall. Based on these findings, we also evaluate H2 metabolism as a possible target for drug development or other therapies.

scholarly journals Hydrogen Metabolism inHelicobacter pyloriPlays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Ge Wang ◽  
Judith Romero-Gallo ◽  
Stéphane L. Benoit ◽  
M. Blanca Piazuelo ◽  
Ricardo L. Dominguez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Respiratory Chain ◽  
Molecular Hydrogen ◽  
Gastric Carcinogenesis ◽  
Hydrogenase Activity ◽  
Hydrogen Metabolism ◽  
Gastric Cancer Risk ◽  
Ags Cells ◽  
H Pylori

ABSTRACTA known virulence factor ofHelicobacter pylorithat 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. A Δhydmutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) was used to specifically inhibit the H2-utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H2-generated transmembrane potential is a contributor to toxin translocation. The Δhydstrain showed a decreased frequency of DNA transformation, suggesting thatH. pylorihydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the Δhydstrain to induce inflammation was significantly attenuated (at 12 weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the Δhydstrain. By examining the hydrogenase activities from well-defined clinicalH. pyloriisolates, we observed that strains isolated from cancer patients (n= 6) have a significantly higher hydrogenase (H2/O2) activity than the strains isolated from gastritis patients (n= 6), further supporting an association betweenH. pylorihydrogenase activity and gastric carcinogenesis in humans.IMPORTANCEHydrogen-utilizing hydrogenases are known to be important for some respiratory pathogens to colonize hosts. Here a gastric cancer connection is made via a pathogen’s (H. pylori) use of molecular hydrogen, a host microbiome-produced gas. Delivery of the known carcinogenic factor CagA into host cells is augmented by the H2-utilizing respiratory chain of the bacterium. The role of hydrogenase in carcinogenesis is demonstrated in an animal model, whereby inflammation markers and cancer development were attenuated in the hydrogenase-null strain. Hydrogenase activity comparisons of clinical strains of the pathogen also support a connection between hydrogen metabolism and gastric cancer risk. While molecular hydrogen use is acknowledged to be an alternative high-energy substrate for some pathogens, this work extends the roles of H2oxidation to include transport of a carcinogenic toxin. The work provides a new avenue for exploratory treatment of some cancers via microflora alterations.

Use of molecular hydrogen as an energy substrate by human pathogenic bacteria

2005 ◽  
Vol 33 (1) ◽  
pp. 83-85 ◽  
Author(s):  
R.J. Maier
Keyword(s):  
Molecular Hydrogen ◽  
Parent Strain ◽  
Pathogenic Bacteria ◽  
Enteric Bacteria ◽  
Sequence Information ◽  
Respiratory Pathway ◽  
Whole Cells ◽  
Yersinia Species ◽  
Hydrogenase Enzymes

Molecular hydrogen is produced as a fermentation by-product in the large intestine of animals and its production can be correlated with the digestibility of the carbohydrates consumed. Pathogenic Helicobacter species (Helicobacter pylori and H. hepaticus) have the ability to use H2 through a respiratory hydrogenase, and it was demonstrated that the gas is present in the tissues colonized by these pathogens (the stomach and the liver respectively of live animals). Mutant strains of H. pylori unable to use H2 are deficient in colonizing mice compared with the parent strain. On the basis of available annotated gene sequence information, the enteric pathogen Salmonella, like other enteric bacteria, contains three putative membrane-associated H2-using hydrogenase enzymes. From the analysis of gene-targeted mutants it is concluded that each of the three membrane-bound hydrogenases of Salmonella enterica serovar Typhimurium are coupled with an H2-oxidizing respiratory pathway. From microelectrode probe measurements on live mice, H2 could be detected at approx. 50 μM levels within the tissues (liver and spleen), which are colonized by Salmonella. The half-saturation affinity of whole cells of these pathogens for H2 is much less than this, so it is expected that the (H2-utilizing) hydrogenase enzymes be saturated with the reducing substrate in vivo. All three enteric NiFe hydrogenase enzymes contribute to virulence of the bacterium in a typhoid fever-mouse model, and the combined removal of all three hydrogenases resulted in a strain that is avirulent and (in contrast with the parent strain) one that is not able to pass the intestinal tract to invade liver or spleen tissue. It is proposed that H2 utilization and specifically its oxidation, coupled with a respiratory pathway, is required for energy production to permit growth and maintain efficient virulence of a number of pathogenic bacteria during infection of animals. These would be expected to include the Campylobacter jejuni, a bacterium closely related to Helicobacter, as well as many enteric bacteria (Escherichia coli, Shigella and Yersinia species).

scholarly journals Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensal E. coli during gut inflammation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elizabeth R Hughes ◽  
Maria G Winter ◽  
Laice Alves da Silva ◽  
Matthew K Muramatsu ◽  
Angel G Jimenez ◽  
...  
Keyword(s):  
Molecular Hydrogen ◽  
Intestinal Inflammation ◽  
Electron Acceptors ◽  
Hydrogen Metabolism ◽  
Bacterial Genomes ◽  
Infectious Colitis ◽  
E Coli ◽  
Genes Encoding ◽  
Inflammatory Bowel ◽  
Hydrogenase 2

The composition of gut-associated microbial communities changes during intestinal inflammation, including an expansion of Enterobacteriaceae populations. The mechanisms underlying microbiota changes during inflammation are incompletely understood. Here, we analyzed previously published metagenomic datasets with a focus on microbial hydrogen metabolism. The bacterial genomes in the inflamed murine gut and in patients with inflammatory bowel disease contained more genes encoding predicted hydrogen-utilizing hydrogenases compared to communities found under non-inflamed conditions. To validate these findings, we investigated hydrogen metabolism of Escherichia coli, a representative Enterobacteriaceae, in mouse models of colitis. E. coli mutants lacking hydrogenase-1 and hydrogenase-2 displayed decreased fitness during colonization of the inflamed cecum and colon. Utilization of molecular hydrogen was in part dependent on respiration of inflammation-derived electron acceptors. This work highlights the contribution of hydrogenases to alterations of the gut microbiota in the context of non-infectious colitis.

scholarly journals The plant pathogenPectobacterium atrosepticumcontains a functional formate hydrogenlyase-2 complex

2019 ◽  
Author(s):  
Alexander J. Finney ◽  
Rebecca Lowden ◽  
Michal Fleszar ◽  
Marta Albareda ◽  
Sarah J. Coulthurst ◽  
...  
Keyword(s):  
Complex I ◽  
Molecular Hydrogen ◽  
Formate Dehydrogenase ◽  
Hydrogen Gas ◽  
Hydrogen Metabolism ◽  
Membrane Domain ◽  
Anaerobic Conditions ◽  
New Model ◽  
Formate Hydrogenlyase ◽  
Genes Encoding

SummaryPectobacterium atrosepticumSCRI1043 is a phytopathogenic gram-negative enterobacterium. Genomic analysis has identified that genes required for both respiration and fermentation are expressed under anaerobic conditions. One set of anaerobically expressed genes is predicted to encode an important but poorly-understood membrane-bound enzyme termed formate hydrogenlyase-2 (FHL-2), which has fascinating evolutionary links to the mitochondrial NADH dehydrogenase (Complex I). In this work, molecular genetic and biochemical approaches were taken to establish that FHL-2 is fully functional inP. atrosepticumand is the major source of molecular hydrogen gas generated by this bacterium. The FHL-2 complex was shown to comprise a rare example of an active [NiFe]-hydrogenase-4 (Hyd-4) isoenzyme, itself linked to an unusual selenium-free formate dehydrogenase in the final complex. In addition, further genetic dissection of the genes encoding the predicted membrane domain of FHL-2 established surprisingly that the majority of genes encoding this domain are not required for physiological hydrogen production activity. Overall, this study presentsP. atrosepticumas a new model bacterial system for understanding anaerobic formate and hydrogen metabolism in general, and FHL-2 function and structure in particular.Significance StatementPectobacterium atrospecticumcontains the genes for the formate hydrogenlyase-2 enzyme, considered the ancient progenitor of mitochondrial respiratory Complex I. In this study, the harnessing ofP. atrosepticumas a new model system for understanding bacterial hydrogen metabolism has accelerated new knowledge in FHL-2 and its component parts. Importantly, those component parts include an unusual selenium-free formate dehydrogenase and a complicated [NiFe]-hydrogenase-4 with a large membrane domain. FHL-2 is established as the major source of molecular hydrogen produced under anaerobic conditions byP. atrospectium, however surprisingly some components of the membrane domain were not essential for this activity.

scholarly journals Hydrogenases and Hydrogen Metabolism of Cyanobacteria

2002 ◽  
Vol 66 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Paula Tamagnini ◽  
Rikard Axelsson ◽  
Pia Lindberg ◽  
Fredrik Oxelfelt ◽  
Röbbe Wünschiers ◽  
...  
Keyword(s):  
Molecular Hydrogen ◽  
Recent Progress ◽  
Gene Products ◽  
Uptake Hydrogenase ◽  
Hydrogen Metabolism ◽  
Nostoc Punctiforme ◽  
Scientific Publications ◽  
Production Of Hydrogen ◽  
Molecular Information ◽  
Pcc 7120

SUMMARY Cyanobacteria may possess several enzymes that are directly involved in dihydrogen metabolism: nitrogenase(s) catalyzing the production of hydrogen concomitantly with the reduction of dinitrogen to ammonia, an uptake hydrogenase (encoded by hupSL) catalyzing the consumption of hydrogen produced by the nitrogenase, and a bidirectional hydrogenase (encoded by hoxFUYH) which has the capacity to both take up and produce hydrogen. This review summarizes our knowledge about cyanobacterial hydrogenases, focusing on recent progress since the first molecular information was published in 1995. It presents the molecular knowledge about cyanobacterial hupSL and hoxFUYH, their corresponding gene products, and their accessory genes before finishing with an applied aspect—the use of cyanobacteria in a biological, renewable production of the future energy carrier molecular hydrogen. In addition to scientific publications, information from three cyanobacterial genomes, the unicellular Synechocystis strain PCC 6803 and the filamentous heterocystous Anabaena strain PCC 7120 and Nostoc punctiforme (PCC 73102/ATCC 29133) is included.

Probiotic Displaces Pathogenic Bacteria

2006 ◽  
Vol 37 (7) ◽  
pp. 48
Author(s):  
ERIK GOLDMAN
Keyword(s):  
Pathogenic Bacteria

Iron and Malaria: Absorption, Efficacy and Safety

2010 ◽  
Vol 80 (45) ◽  
pp. 279-292 ◽  
Author(s):  
Richard Hurrell
Keyword(s):  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Malarial Parasite ◽  
Asymptomatic Malaria ◽  
Iron Supplements ◽  
Fortified Food ◽  
Care Giving ◽  
Single Meal ◽  
Women And Children

Febrile malaria and asymptomatic malaria parasitemia substantially decrease iron absorption in single-meal, stable isotope studies in women and children, but to date there is no evidence of decreased efficacy of iron-fortified foods in malaria-endemic regions. Without inadequate malarial surveillance or health care, giving iron supplements to children in areas of high transmission could increase morbidity and mortality. The most likely explanation is the appearance of non-transferrin-bound iron (NTBI) in the plasma. NTBI forms when the rate of iron influx into the plasma exceeds the rate of iron binding to transferrin. Two studies in women have reported substantially increased NTBI with the ingestion of iron supplements. Our studies confirm this, but found no significant increase in NTBI on consumption of iron-fortified food. It seems likely that the malarial parasite in hepatocytes can utilize NTBI, but it cannot do so in infected erythrocytes. NTBI however may increase the sequestration of parasite-infected erythrocytes in capillaries. Bacteremia is common in children with severe malaria and sequestration in villi capillaries could lead to a breaching of the intestinal barrier, allowing the passage of pathogenic bacteria into the systemic circulation. This is especially important as frequent high iron doses increase the number of pathogens in the intestine at the expense of the barrier bacteria.

Sign in / Sign up

Export Citation Format

Share Document