Antivitamins are substances that inhibit the biological function of a genuine vitamin. Some antivitamins have a similar chemical structure to those of the actual vitamin whose action they block or restrict. For this study, Professor Kai Tittmann’s team from the Göttingen Center for Molecular Biosciences at the University of Göttingen worked together with Professor Bert de Groot’s group from the Max Planck Institute for Biophysical Chemistry Göttingen and Professor Tadgh Begley from Texas A&M University (USA). Together they investigated the mechanism of action at the atomic level of a naturally occurring antivitamin of vitamin B1. Some bacteria are able to produce a toxic form of this vital vitamin B1 to kill competing bacteria. This particular antivitamin has only a single atom in addition to the natural vitamin in a seemingly unimportant place and the exciting research question was why the action of the vitamin was still prevented or “poisoned.”

Tittmann’s team used high-resolution protein crystallography to investigate how the antivitamin inhibits an important protein from the central metabolism of bacteria. The researchers found that the “dance of the protons,” which can normally be observed in functioning proteins, almost completely ceases to function and the protein no longer works. “Just one extra atom in the antivitamin acts like a grain of sand in a complex gear system by blocking its finely tuned mechanics,” explains Tittmann. It is interesting to note that human proteins are able to cope relatively well with the antivitamin and continue working. The chemist de Groot and his team used computer simulations to find out why this is so. “The human proteins either do not bind to the antivitamin at all or in such a way that they are not ‘poisoned’,” says the Max Planck researcher. The difference between the effects of the antivitamin on bacteria and on human proteins opens up the possibility of using it as an antibiotic in the future and thus creating new therapeutic alternatives.

The research project was funded by the German Research Foundation (DFG).

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An analysis of viruses in the guts of healthy Westerners also showed that dips and peaks in the diversity of virus types between childhood and old age mirror bacterial changes over the course of the lifespan.

The Gut Virome Database developed by Ohio State University scientists identifies 33,242 unique viral populations that are present in the human gut. (A collection of viruses like those in the human gut is called a virome.) This is not cause for alarm: Most viruses don’t cause disease.

In fact, the more scientists learn about viruses, the more they see them as part of the human ecosystem — suggesting viruses have potential to represent a new class of drugs that could fight disease-causing bacteria, especially those resistant to antibiotics. Better knowledge of viruses in the gut environment could even improve understanding of the gastrointestinal symptoms experienced by some of the sickest COVID-19 patients.

The researchers plan to update the open-access database on a regular basis.

“We’ve established a robust starting point to see what the virome looks like in humans,” said study co-author Olivier Zablocki, a postdoctoral researcher in microbiology at Ohio State. “If we can characterize the viruses that are keeping us healthy, we might be able to harness that information to design future therapeutics for pathogens that can’t otherwise be treated with drugs.”

The study is published today (Aug. 24) in the journal Cell Host & Microbe.

Talk of the good and bad bacteria in the gut microbiome is commonplace these days, but viruses in the gut — and everywhere — are hard to detect because their genomes don’t contain a common signature gene sequence that bacteria genomes do. So much of the vast sequence space of viruses remains unexplored that it is often referred to as “dark matter.”

For this work, the researchers started with data from 32 studies over about a decade that had looked at gut viruses in a total of 1,986 healthy and sick people in 16 countries. Using techniques to detect virus genomes, the team identified more than 33,000 different viral populations.

“We used machine learning on known viruses to help us identify the unknown viruses,” said first author Ann Gregory, who completed this work while she was a graduate student at Ohio State. “We were interested in how many types of viruses we could see in the gut, and we determined that by how many types of genomes we could see since we couldn’t visually see the viruses.”

Their analysis confirmed findings from smaller studies suggesting that though a few viral populations were shared within a subset of people, there is no core group of gut viruses common to all humans.

A few trends were identified, however. In healthy Western individuals, age influences the diversity of viruses in the gut, which increases significantly from childhood to adulthood, and then decreases after age 65. The pattern matches what is known about ebbs and flows of gut bacterial diversity with one exception: Infant guts with underdeveloped immune systems are teeming with a range of virus types, but few bacteria varieties.

People living in non-Western countries had higher gut virus diversity than Westerners. Gregory said other research has shown that non-Western individuals who move to the United States or another Western country lose that microbiome diversity, suggesting diet and environment drive virome differences. (For example, the scientists found some intact plant viruses in the gut — the only way for them to get there is through the diet.) Variations in viral diversity could also be seen in healthy versus sick participants in the 32 studies analyzed.

“A general rule of thumb for ecology is that higher diversity leads to a healthier ecosystem,” Gregory said. “We know that more diversity of viruses and microbes is usually associated with a healthier individual. And we saw that healthier individuals tend to have a higher diversity of viruses, indicating that these viruses may be potentially doing something positive and having a beneficial role.”

Almost all of the populations — 97.7 percent — were phages, which are viruses that infect bacteria. Viruses have no function without a host — they drift in an environment until they infect another organism, taking advantage of its properties to make copies of themselves. The most-studied viruses kill their host cells, but scientists in the Ohio State lab in which Gregory and Zablocki worked have discovered more and more phage-type viruses that coexist with their host microbes and even produce genes that help the host cells compete and survive.

The leader of that lab, senior study author Matthew Sullivan, has his sights set on “phage therapy” — the 100-year-old idea of using phages to kill antibiotic-resistant pathogens or superbugs.

“Phages are part of a vast interconnected network of organisms that live with us and on us, and when broad-spectrum antibiotics are used to fight against infection, they also harm our natural microbiome,” Sullivan said. “We are building out a toolkit to scale our understanding and capabilities to use phages to tune disturbed microbiomes back toward a healthy state.

“Importantly, such a therapeutic should impact not only our human microbiome, but also that in other animals, plants and engineered systems to fight pathogens and superbugs. They could also provide a foundation for something we might have to consider in the world’s oceans to combat climate change.”

A professor of microbiology and civil, environmental and geodetic engineering, Sullivan has helped establish cross-disciplinary research collaborations at Ohio State. He recently founded and directs Ohio State’s new Center of Microbiome Science and co-directs the Infectious Diseases Institute’s Microbial Communities program.

Zablocki noted that there is still a lot to learn about the functions of viruses in the gut — both beneficial and harmful.

“I see it as the chicken and the egg,” he said. “We see the disease and we see the community structure. Was it because of this community structure that the disease occurred, or is the disease causing the community structure that we see? This standardized dataset will enable us to pursue those questions.”

This work was supported by the Ohio Supercomputer Center and funded by the Gordon and Betty Moore Foundation, the National Institutes of Health and Ohio State’s Center of Microbiome Science.

The device, developed by a team from the University of Cambridge, is a significant step toward achieving artificial photosynthesis — a process mimicking the ability of plants to convert sunlight into energy. It is based on an advanced ‘photosheet’ technology and converts sunlight, carbon dioxide and water into oxygen and formic acid — a storable fuel that can be either be used directly or be converted into hydrogen.

The results, reported in the journal Nature Energy, represent a new method for the conversion of carbon dioxide into clean fuels. The wireless device could be scaled up and used on energy ‘farms’ similar to solar farms, producing clean fuel using sunlight and water.

Harvesting solar energy to convert carbon dioxide into fuel is a promising way to reduce carbon emissions and transition away from fossil fuels. However, it is challenging to produce these clean fuels without unwanted by-products.

“It’s been difficult to achieve artificial photosynthesis with a high degree of selectivity, so that you’re converting as much of the sunlight as possible into the fuel you want, rather than be left with a lot of waste,” said first author Dr Qian Wang from Cambridge’s Department of Chemistry.

“In addition, storage of gaseous fuels and separation of by-products can be complicated — we want to get to the point where we can cleanly produce a liquid fuel that can also be easily stored and transported,” said Professor Erwin Reisner, the paper’s senior author.

In 2019, researchers from Reisner’s group developed a solar reactor based on an ‘artificial leaf’ design, which also uses sunlight, carbon dioxide and water to produce a fuel, known as syngas. The new technology looks and behaves quite similarly to the artificial leaf but works in a different way and produces formic acid.

While the artificial leaf used components from solar cells, the new device doesn’t require these components and relies solely on photocatalysts embedded on a sheet to produce a so-called photocatalyst sheet. The sheets are made up of semiconductor powders, which can be prepared in large quantities easily and cost-effectively.

In addition, this new technology is more robust and produces clean fuel that is easier to store and shows potential for producing fuel products at scale. The test unit is 20 square centimetres in size, but the researchers say that it should be relatively straightforward to scale it up to several square metres. In addition, the formic acid can be accumulated in solution, and be chemically converted into different types of fuel.

“We were surprised how well it worked in terms of its selectivity — it produced almost no by-products,” said Wang. “Sometimes things don’t work as well as you expected, but this was a rare case where it actually worked better.”

The carbon-dioxide converting cobalt-based catalyst is easy to make and relatively stable. While this technology will be easier to scale up than the artificial leaf, the efficiencies still need to be improved before any commercial deployment can be considered. The researchers are experimenting with a range of different catalysts to improve both stability and efficiency.

The current results were obtained in collaboration with the team of Professor Kazunari Domen from the University of Tokyo, a co-author of the study.

The researchers are now working to further optimise the system and improve efficiency. Additionally, they are exploring other catalysts for using on the device to get different solar fuels.

“We hope this technology will pave the way toward sustainable and practical solar fuel production,” said Reisner.