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Salmonella uses the enzyme S. Tm hyb hydrogenase, to facilitates
consumption of hydrogen (H2) to power its growth.
Introducing hydrogen, H2, consuming bacteria into
the intestine interfered with hyb expansion.
Therefore, H2 is an Achilles’ heel to Salmonella infection
and might offer an opportunity to prevent infection.
The intestine is bustling with billions of intestinal bacteria that aid digestion and keep it healthy. A vast array of microorganisms (microbiota) colonise the intestine so densely that pathogens do not usually stand a chance of multiplying.
Some pathogens, such as the diarrhoea-causing bacterium Salmonella Typhimurium, still manage to invade the densely populated intestinal ecosystem. Researchers at ETH Zurich are a step closer to finding out how they do this and along the way, discovered where the pathogen obtains the energy from for its attack on the intestinal biota.
Wolf-Dietrich Hardt, Professor of Microbiology at ETH Zürich, together with his PhD student Lisa Maier, examined which factors play a role in the early stages of a Salmonella attack.
During the invasion of the intestinal ecosystem, Salmonella Typhimurium uses an enzyme that helps it to assert itself against microbiota: the hydrogenase enzyme, which converts hydrogen into energy.
"Although we already knew that Salmonella Typhimurium can use hydrogen in addition to many other sources of energy, it was not clear which source of energy it used during this early stage of intestinal colonisation," explains Maier.
Theft-based hydrogen economy
Hydrogen is created in the intestine as a chemical intermediate of the microbiota's normal metabolism.
"Salmonella therefore operates a theft-based hydrogen economy by stealing energy from the microbiota to assert itself," says Hardt. Because the microbiota metabolism of most animals works in a similar way, the pathogen can find the necessary energy source for its initial attack in any new animal host.
Once Salmonella Typhimurium has managed to multiply inside the intestine, the bacterium invades the intestinal tissue and causes infection and diarrhoea. In some cases, Salmonella Typhimurium even finds its way into the bloodstream and internal organs.
However, animal experiments have shown that the energy boost from hydrogen does not play an essential role during this process. "Outside the intestinal lumen, Salmonella Typhimurium does not have to create space for itself in a dense community of microorganisms," explains Maier.
The Achilles' heel of intestinal flora
The hydrogenase enzyme is also found in other bacteria, such as Escherichia coli and Helicobacter pylori, which cause stomach ulcers. The researchers therefore suspect that other pathogens also use the hydrogen produced by intestinal flora as a source of energy. This would make the microbiota's own metabolism an Achilles' heel in the defence against a range of germs.
"The purpose of intestinal flora is to protect against infection. However, we are now seeing for the first time that it can also facilitate infections by serving as an unintentional energy provider."
Wolf-Dietrich Hardt, Professor of Microbiology, ETH Zürich
The interaction between microbiota and pathogens is thus more complex than initially thought.
The work is published
in Cell Host & Microbe, December 11, 2013. DOI: 10.1016/j.chom.2013.11.002, titled: Microbiota-Derived Hydrogen Fuels Salmonella Typhimurium Invasion of the Gut Ecosystem.
Initially, S. Typhimurium (S. Tm) grows in the unperturbed gut (ecosystem invasion)
S. Tm hyb hydrogenase is required for ecosystem invasion
Hyb allows S. Tm to use microbiota-derived hydrogen as an energy source
Subversion of a microbiota metabolite fuels gut ecosystem invasion by S. Tm
The intestinal microbiota features intricate metabolic interactions involving the breakdown and reuse of host- and diet-derived nutrients. The competition for these resources can limit pathogen growth. Nevertheless, some enteropathogenic bacteria can invade this niche through mechanisms that remain largely unclear. Using a mouse model for Salmonella diarrhea and a transposon mutant screen, we discovered that initial growth of Salmonella Typhimurium (S. Tm) in the unperturbed gut is powered by S. Tm hyb hydrogenase, which facilitates consumption of hydrogen (H2), a central intermediate of microbiota metabolism. In competitive infection experiments, a hyb mutant exhibited reduced growth early in infection compared to wild-type S. Tm, but these differences were lost upon antibiotic-mediated disruption of the host microbiota. Additionally, introducing H2-consuming bacteria into the microbiota interfered with hyb-dependent S. Tm growth. Thus, H2 is an Achilles’ heel of microbiota metabolism that can be subverted by pathogens and might offer opportunities to prevent infection.
Maier L, Vyas R, Cordova CD, Lindsay H, Schmidt TSB, Brugiroux S, Periaswamy B, Bauer R, Sturm A, Schreiber F, von Mering C, Robinson MD, Stecher B, Hardt WD: Microbiota-Derived Hydrogen Fuels Salmonella Typhimurium Invasion of the Gut Ecosystem.