2005 · Maier — Use of molecular hydrogen as an energy substrate by human pathogenic bacteria
Super-Abstract
Several pathogenic bacteria — including Helicobacter pylori (stomach), Helicobacter hepaticus (liver), and Salmonella — can use molecular hydrogen (H₂) produced in the gut as a respiratory fuel, and this ability significantly enhances their capacity to colonise and cause disease in animals. This is a microbiology/animal study — not a human clinical study, and not about H₂ supplementation as a health intervention.
Commentary
This animal and in-vitro microbiology paper investigates how gut-produced H₂ fuels bacterial virulence. H₂ gas is generated in the large intestine by fermentation of dietary carbohydrates. Maier shows that H. pylori and H. hepaticus each possess a respiratory hydrogenase enzyme that allows them to oxidise H₂ for energy — and that H₂ is detectable (~50 µM) in the tissues these pathogens colonise (stomach, liver, spleen in live mouse models). Mutant H. pylori strains that cannot use H₂ are significantly less able to colonise mouse stomachs. In Salmonella, three membrane-bound NiFe hydrogenases all contribute to virulence in a typhoid fever mouse model; strains lacking all three are avirulent and cannot pass through the intestinal tract to invade liver or spleen. The paper proposes that H₂ oxidation is a key energy source for multiple enteric and gastric pathogens. This is a fundamentally different context from therapeutic or dietary H₂ — here H₂ benefits the pathogen, not the host.
Key quotes
- „Mutant strains of H. pylori unable to use H(2) are deficient in colonizing mice compared with the parent strain.“ — H₂ utilisation by the pathogen directly enhances its ability to infect the host (mouse model)
- „All three enteric NiFe hydrogenase enzymes contribute to virulence of the bacterium in a typhoid fever-mouse model.“ — H₂-metabolising enzymes are virulence factors in Salmonella — animal model
- „H(2) 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.“ — the authors' central conclusion: H₂ fuels bacterial virulence, not host protection
Our assessment
An animal/in-vitro microbiology study showing that gut-produced H₂ fuels the virulence of several pathogenic bacteria (H. pylori, H. hepaticus, Salmonella) in mouse models. This is not a study of H₂ as a health supplement or therapeutic agent — the H₂ here benefits the bacteria, not the host. These findings do not contradict beneficial H₂ effects in other contexts, but they add important biological complexity: H₂ in the gut is a substrate used by multiple microorganisms, including pathogens. Findings are from animal/cell experiments and cannot be directly extrapolated to human H₂ supplementation outcomes.
Study design
- Type: animal study (mouse models) + in-vitro biochemistry · Organisms: H. pylori, H. hepaticus (mice); Salmonella enterica Typhimurium (typhoid fever mouse model) · H₂ source: endogenous gut fermentation; microelectrode measurements in live mice
- Result: H₂-utilisation-deficient H. pylori mutants show impaired colonisation; all three Salmonella NiFe hydrogenases contribute to virulence; combined triple-hydrogenase deletion renders Salmonella avirulent in mice
Abstract
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 H(2) 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 H(2) 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 H(2)-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 H(2)-oxidizing respiratory pathway. From microelectrode probe measurements on live mice, H(2) could be detected at approx. 50 muM levels within the tissues (liver and spleen), which are colonized by Salmonella. The half-saturation affinity of whole cells of these pathogens for H(2) is much less than this, so it is expected that the (H(2)-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 H(2) 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).
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