Large viruses plagued by human intestinal bacteria



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The bacteria cut fragments of the invading phage genome and store them in their CRISPR systems in order to detect and kill future invaders. Credit: University of California – Berkeley

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

According to a new study conducted by scientists at the University of California at Berkeley, some of the most important of these so-called bacteriophages have now been found in the intestine, periodically devastating bacteria.

These "megaphages" – which have genomes approximately 10 times larger than the average phage and twice as large as any previously found phage in humans – have been found 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, or even be carriers of diseases.

"Phage are well known for carrying genes that cause diseases and genes that code for antibiotic resistance," said Jill Banfield, who leads the microbiological initiative of the Innovative Genomics Institute and is a professor at the University of Berkeley 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 because megaphages, which most biologists do not consider "alive," are larger than life forms such as bacteria, they lessen the distinction between what is alive and what is not.

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

Banfield and his colleagues reported their findings online on January 28 in the newspaper Microbiology of nature.

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 of 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 group or megaphage 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 very likely that these phages are moving across animal cohorts," Banfield said. "We suspect that baboons have recently acquired the Prevotella and Lak phages because they resist so little and that they are widespread 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 phage populations and the bacteria they feed on in the gut evolve over time and with diet, 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 in order to produce the proteins needed to prevent the bacterial host from interfering with the phage's 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 unimagined processes to date, there is a lot of new biology to discover in these new genomes," she said.


Explore further:
CRISPR-Cas9 can be a double-edged sword for bacteria

More information:
Audra E. Devoto et al., Megaphages infect Prevotella and its variants are widespread in intestinal microbiomes. Microbiology of nature (2019). DOI: 10.1038 / s41564-018-0338-9

Journal reference:
Microbiology of nature

Provided by:
University of California, Berkeley

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