Virus World

While glacier ice cores provide climate information over tens to hundreds of thousands of years, study of microbes is challenged by ultra-low-biomass conditions, and virtually nothing is known about co-occurring viruses. Here we establish ultra-clean microbial and viral sampling procedures and apply them to two ice cores from the Guliya ice cap (northwestern Tibetan Plateau, China) to study these archived communities. This method reduced intentionally contaminating bacterial, viral, and free DNA to background levels in artificial-ice-core control experiments, and was then applied to two authentic ice cores to profile their microbes and viruses. The microbes differed significantly across the two ice cores, presumably representing the very different climate conditions at the time of deposition that is similar to findings in other cores. 

Separately, viral particle enrichment and ultra-low-input quantitative viral metagenomic sequencing from ∼520 and ∼15,000 years old ice revealed 33 viral populations (i.e., species-level designations) that represented four known genera and likely 28 novel viral genera (assessed by gene-sharing networks). In silico host predictions linked 18 of the 33 viral populations to co-occurring abundant bacteria, including Methylobacterium,  Sphingomonas, and Janthinobacterium, indicating that viruses infected several abundant microbial groups. Depth-specific viral communities were observed, presumably reflecting differences in the environmental conditions among the ice samples at the time of deposition.

Together, these experiments establish a clean procedure for studying microbial and viral communities in low-biomass glacier ice and provide baseline information for glacier viruses, some of which appear to be associated with the dominant microbes in these ecosystems.

Published in bioRxiv (January 7, 2020):

https://doi.org/10.1101/2020.01.03.894675

Most of the viruses present in people’s guts are bacteriophages, but how they interact with resident bacteria is still an open question. There’s a lot that scientists don’t know about the gut microbiota, and when it comes to the viruses present there they know even less. To learn more, researchers have monitored the gut viromes of nine people for a full year and that of one person for more than two years. They find that many types of bacteriophages are present and that each individual’s virome is stable over time and different from that of the other subjects.

This study “generates an important database for phages in the gut,” says Corrine Maurice, a microbiologist at McGill University who did not participate in the work. “That’s a database that we just didn’t have, and so that data is going to allow us to formulate some really cool hypotheses going forward. It’s really providing us with tools to . . . look further into what these phages may be doing for our health. “It confirms recent reports that there is no such thing as a core gut virome shared between adult individuals, which is in contrast with the bacterial component of our microbiota where there are more members shared between humans,” Evelien Adriaenssens, who studies gut viruses at the Quadram Institute in the UK and was not involved in the work, writes in an email to The Scientist. “We need more studies on the gut virome like these to establish a baseline about what a healthy human gut virome looks like, taking into account differences in for example geography, ethnicity and lifestyle. After we know what is healthy, we can start looking at complex disease syndromes . . . and identify what changes in the virome can be used as a marker for disease.”

There’s a lot that scientists don’t know about the gut microbiota, and when it comes to the viruses present there they know even less. To learn more, researchers have monitored the gut viromes of nine people for a full year and that of one person for more than two years. They find that many types of bacteriophages are present and that each individual’s virome is stable over time and different from that of the other subjects.

This study “generates an important database for phages in the gut,” says Corrine Maurice, a microbiologist at McGill University who did not participate in the work. “That’s a database that we just didn’t have, and so that data is going to allow us to formulate some really cool hypotheses going forward. It’s really providing us with tools to . . . look further into what these phages may be doing for our health.”

“It confirms recent reports that there is no such thing as a core gut virome shared between adult individuals, which is in contrast with the bacterial component of our microbiota where there are more members shared between humans,” Evelien Adriaenssens, who studies gut viruses at the Quadram Institute in the UK and was not involved in the work, writes in an email to The Scientist. “We need more studies on the gut virome like these to establish a baseline about what a healthy human gut virome looks like, taking into account differences in for example geography, ethnicity and lifestyle. After we know what is healthy, we can start looking at complex disease syndromes . . . and identify what changes in the virome can be used as a marker for disease.”

Andrey Shkoporov, a microbiologist at University College Cork, and colleagues set out to establish that baseline. “We thought, ‘Okay, before we embark on comparative studies of the virome in different health conditions, why don’t we look at the longitudinal stability and inter-individual variability of the gut virome between healthy human subjects,’” he tells The Scientist. 

The research team collected fecal samples from 10 adults—four men and six women—every month for a year. From one female subject, they collected three additional samples at months 19, 20, and 26. Then they separated viral particles from fecal matter and cells and isolated and sequenced viral nucleic acids. Because 99 percent of gut viruses are unknown to science, Shkoporov says, it was not possible to rely on existing viral sequence databases to figure out what was there. Instead, the authors assembled the reads into overlapping DNA sequences, predicted protein coding genes, and then tried to detect any similarities between proteins in databases with those likely encoded by the long stretches of DNA. “This can help to get a rough idea what kind of viruses we are dealing with,” Shkoporov adds. The researchers reported yesterday (October 9) in Cell Host & Microbe  that the individual viromes were stable over the 12 or 26 months of the study and diverse, meaning there were many types of bacteriophages present. While the subjects’ viral communities stayed consistent over time, each person’s complement of gut viruses looked different from that of the others.....

Published in Cell Host & Microbe on October 9, 2019:

https://doi.org/10.1016/j.chom.2019.09.009

A study released today in Nature Microbiology reveals patterns of a virus that half the people in the world are carrying. The collaboration of 117 scientists across the globe focuses on crAssphage, a virus that feeds on human gut bacteria.

Scientists discovered crAssphage when a DNA sequence repeatedly showed up using a genomics technique called cross-assembly. Researchers have previously known that there are many different viruses in the human gut. However, they have never seen one as widespread as crAssphage. 

Since crAssphage is a virus found in the human gut, sampling sewage in wastewater treatment plants is one of the most efficient ways to find diverse crAssphage strains in one geographic region. Using this method, the scientists analyzed more than 32,000 crAssphage sequences distributed across 67 countries in every continent besides Antarctica. The study examined individuals and their crAssphage. The scientists found a child in the U.S. that had 1,409 different strains and an infant in Finland with 748 strains of crAssphage.

The study was published today in Nature Microbiology: 

https://doi.org/10.1038/s41564-019-0494-6

The fight against drug-resistant pathogens remains an intense one. While the Centers for Disease Control's (CDC) 2019 "biggest threats" report reveals an overall decrease in drug-resistant microbe-related deaths as compared to its previous report (2013) the agency also cautions that new forms of drug-resistant pathogens are still emerging. Meanwhile, the options for treating infections by these germs are diminishing, confirming doctors' and scientists' worries about the end of the age of antibiotics.

"We knew it was going to be a problem early on," said UC Santa Barbara chemistry and biochemistry professor Irene Chen. "Basically as soon as penicillin was discovered, a few years later it was reported that there was a resistant organism." Thanks to factors such as horizontal gene transfer and rapid reproduction, organisms such as Gram-negative bacteria are able to evolve faster than we can produce antibiotics to control them. So Chen and her research group are seeking alternatives to antibiotics, in a growing effort to head off the tide of incurable bacterial infections. In their work, the group has turned to bacteriophages, a naturally occurring group of viruses that colonize on bacteria. "That's their natural function, really, to grow on and kill bacteria," said Chen, author of a paper that appears in the Proceedings of the National Academy of Sciences. By taking advantage of the bacteriophages' ability to home in on specific bacteria without damaging the rest of the microbiome, the researchers were able to use a combination of gold nanorods and near-infrared light to destroy even multidrug-resistant bacteria without antibiotics. Phage therapy isn't new, Chen said. In fact, it have been used in the former Soviet Union and Europe for about a century, though they are seen largely as last-resort alternatives to antibiotics. Among the unresolved issues of phage therapy is the incomplete characterization of the phages' biology—a biology that could allow for unintended consequences due to the phages' own rapid evolution and reproduction, as well as potential toxins the viruses may carry. Another issue is the all-or-nothing aspect of phage therapy, she added. "It's difficult to analyze the effect of a phage treatment," she said. "You might see it completely work or you might see it completely fail, but you don't have the kind of dose response you want."

To surmount these challenges, the Chen lab developed a method of controlled phage therapy. "What we did was to conjugate the phages to gold nanorods," she explained. These "phanorods" were applied to bacteria on in-vitro cultures of mammalian cells and then exposed to near-infrared light. "When these nanorods are photo-excited, they translate the energy from light to heat," Chen said, "and that creates very high local temperatures." The heat is enough to kill the bacteria, and it also kills the phages, preventing any unwanted further evolutions. The result is a guided missile of targeted phage therapy that also allows for dosage control. The lab found success in destroying E. coli, P. aeruginosa and V. cholerae—human pathogens that cause acute symptoms if left unchecked. They also were able to successfully destroy X. campestris, a bacteria that causes rot in plants....

Published in PNAS (January 13, 2020):

https://doi.org/10.1073/pnas.1913234117