Intestinal bacteria in the grip of giant viruses

Viruses attack bacteria just as viruses like the flu hit humans.

According to a new study by scientists at the University of Berkeley, some of the largest of these so-called bacteriophages have now been found in the human gut, periodically devastating bacteria, while seasonal epidemics of influenza threaten humans, revealed low human mortality.

These "megaphages" – whose genomes are about 10 times larger than the average phage and twice as large as any previously observed phage in humans – have been discovered in the human intestinal tract, but only in humans who feed on non-western fibers rich in fiber. , low fat diet.

Tellingly, they have also been found in the intestines of baboons and a pig, demonstrating that phages, carriers of genes that affect human health, can move between humans and animals and possibly even cause diseases.

"Phage are well known for carrying genes that cause diseases and genes that code for antibiotic resistance," said Jill Banfield, who leads the microbiology initiative of the Innovative Genomics Institute and is a professor at the Berkeley University on earth sciences and planets and environmental sciences. and management. "The movement of megaphages with the movement of the host bacteria raises the possibility that the disease can also be transmitted between animals and humans, and that the ability to do so for megaphages is much greater."

And since most biologists do not consider viruses to be "alive," the fact that megaphages are larger than life forms, such as bacteria, blurs the distinction between what is alive and what is not. not.

"These huge entities bridge the gap between what we consider to be non-life and life, and in a sense, we mostly missed them," Banfield said.

Banfield and his colleagues reported their findings online on January 28 in the journal Nature Microbiology.

Phages and CRISPR

Banfield is a pioneer in metagenomic sequencing, which is the simultaneous sequencing of all soup genes of all organisms in a community. She and her colleagues then rebuild the genomes of each creature in the community, revealing microbes never seen before. Exploring microbial communities in mine runoff, geysers, the human intestinal tract and underground depths, she discovered so many new microbes through metagenomic sequencing that the tree of life had to be redesigned to accommodate them all.

During this process, she discovered many bacteriophage genes, phages being officially known. In fact, the CRISPR group present in certain bacteria is a reservoir of fragments of the phage genome that these bacteria retain to remind them of previous phage infections, allowing them to rapidly fight against subsequent infections by the same phage. The Cas9 protein mobilized by these bacteria to target and reduce viral invaders has been adapted by scientists at the University of Berkeley and Vienna to form a powerful tool, CRISPR-Cas9, that has revolutionized biology and revitalized the field of genetical therapy.

In the Sequencing of Intestinal Bacteria Among People in Bangladesh – in a study by University College London collaborator Joanne Santini – to explore the effects of arsenic-contaminated water on flora intestinal – Banfield identified these megaphages. Once she rebadembled their entire genomes, she found that they were all 10 times larger than the average phage encountered in other microbiomes. To accommodate the inflated genomes of these phages, their packaging, called capsid, is probably larger than those of other known phages, which may have a width between 200 and 300 nanometers.

She and her colleagues discovered a CRISPR segment in a type of bacterium, Prevotella, which contained megaphage DNA extracts, suggesting that the megaphage attacks mainly at Prevotella. Prevotella is not common among people with a Westernized diet, with a lot of meat, fat and sugar, and fewer intestinal microbiomes from those consuming a non-western "hunter-gatherer" diet have been sequenced .

Prevotella is also badociated with upper respiratory tract infections and is prevalent in periodontal diseases, according to coauthor Joanne Santini. This means that the new megaphage could pave the way for the development of new phage treatments for infections caused by Prevotella.

Hunter-gatherer microbiomes

Banfield and his team named the mega-phage group or clade "phage lak" after the Bangladesh region where they found them, Laksam Upazila. Subsequently, the first author, Audra Devoto, found Lak phages in intestinal microbiomes of members of the Hadza tribe of hunter-gatherers in Tanzania, in two distinct social groups of baboons studied in Kenya and in the intestinal microbiota of pigs. Danish farms.

"Lak phages in pigs are closer to humans than baboons, so it's quite likely that these phages will cross cohorts of animals," Banfield said. "We suspect that baboons have recently purchased the Prevotella and Lak phages, because they have so little resistance and they are so prevalent among them."

Phage are known to carry genes that exacerbate many human diseases. They can carry genes coding for botulism, toxins of cholera and diphtheria, which aggravates the symptoms of people infected with the bacteria. One of Banfield's goals is to see how the phage and bacteria populations that they feed in the gut evolve over time and with food, as well as their health effects.

In the four humans whose intestinal microbiomes were sampled, the team found that phage and Prevotella levels evolved over time, indicating a constant cycle in which increasing populations of phages lower bacterial populations, followed by fall of the phage allowing Prevotella to rebound.

Banfield badumes that megaphages have larger genomes to produce the proteins needed to prevent the bacterial host from interfering with phage efforts to multiply, which takes longer because of the larger genome.

Banfield and its laboratory at the innovative Genomics Institute, a joint UC / Berkeley / UCSF initiative to widely deploy CRISPR-Cas9, are looking for megaphages in other metagenomic databases and hope to find out more more about how they work and their potential. the proteins.

"These genomes are full of proteins of unknown function, probably pathways for processes not imagined to date. There is a lot of new biology to discover in these new genomes, "she said.

This article has been republished from documents provided by the University of California at Berkeley. Note: Content may have changed for length and content. For more information, please contact the cited source.

Reference
Megaphages infect Prevotella and its variants are widespread in intestinal microbiomes. Audra E. Devoto, Joanne M. Santini, Matthew R. Olm, Karthik Anantharaman, Patrick Munk, Jenny Tung, Elizabeth A. Archie, Peter Turnbaugh, Kimberley D. Seed, Ran Blekhman, Frank M. Aarestrup, Brian C. Thomas and Jillian F. Banfield. Nature Microbiology (2019), https://doi.org/10.1038/s41564-018-0338-9.